PROBLEM/CONDITION: At the end of 2009, an estimated 1,148,200 persons aged ≥13 years were living with human immunodeficiency virus (HIV) infection in the United States. Despite the recent decreases in HIV infection attributed to injection drug use, 8% of new HIV infections in 2010 occurred among injecting drug users (IDUs). REPORTING PERIOD: June-December 2009. DESCRIPTION OF SYSTEM: The National HIV Behavioral Surveillance System (NHBS) collects HIV prevalence and risk behavior data in selected metropolitan statistical areas (MSAs) from three populations at high risk for HIV infection: men who have sex with men, IDUs, and heterosexual adults at increased risk for HIV infection. Data for NHBS are collected in rotating cycles. For the 2009 NHBS cycle, IDUs were recruited in 20 participating MSAs using respondent-driven sampling, a peer-referral sampling method. Participants were eligible if they were aged ≥18 years, lived in a participating MSA, were able to complete a behavioral survey in English or Spanish, and reported that they had injected drugs during the past 12 months. Consenting participants completed an interviewer-administered (face-to-face), anonymous standardized questionnaire about HIV-associated behaviors, and all participants were offered anonymous HIV testing. Analysis of 2009 NHBS data represents the first large assessment of HIV prevalence among IDUs in the United States in >10 years. RESULTS: This report summarizes two separate analyses using unweighted data from 10,200 eligible IDUs in 20 MSAs from the second collection cycle of NHBS in 2009. Both an HIV infection analysis and a behavioral analysis were conducted. Different denominators were used in each analysis because of the order and type of exclusion criteria applied. For the HIV infection analysis, of the 10,200 eligible participants, 10,090 had a valid HIV test result, of whom 906 (9%) tested positive for HIV (range: 2%-19% by MSA). When 509 participants who reported receiving a previous positive HIV test result were excluded from this analysis, 4% (397 of 9,581 participants) tested HIV-positive. For the behavioral analysis, because knowledge of HIV status might influence risk behaviors, 548 participants who reported a previous HIV-positive test result were excluded from the 10,200 eligible participants. All subsequent analyses were conducted for the remaining 9,652 participants. The most commonly injected drugs during the past 12 months among these participants were heroin (90%), speedball (heroin and cocaine combined) (58%), and cocaine or crack (49%). Large percentages of participants reported receptive sharing of syringes (35%); receptive sharing of other injection equipment, such as cookers, cotton, or water (58%); and receptive sharing of syringes to divide drugs (35%). Many participants reported having unprotected sex with opposite-sex partners during the past 12 months: 70% of men and 73% of women had unprotected vaginal sex, and 25% of men and 21% of women had unprotected anal sex. A combination of unsafe injection- and sex-related behaviors during the past 12 months was commonly reported; 41% of participants who reported unprotected vaginal sex with one or more opposite-sex partners, and 53% of participants who reported unprotected anal sex with one or more opposite-sex partners also reported receptive sharing of syringes. More women than men reported having sex in exchange for money or drugs (31% and 18%, respectively). Among men, 10% had oral or anal sex with one or more male partners during the past 12 months. Many participants (74%) reported noninjection drug use during the past 12 months, and 41% reported binge drinking during the past 30 days. A large percentage of participants (74%) had ever been tested for hepatitis C, 41% had received a hepatitis C virus infection diagnosis, and 29% had received a vaccination against hepatitis A virus, hepatitis B virus, or both. Most (88%) had been tested for HIV during their lifetime, and 49% had been tested during the past 12 months. Approximately half of participants received free HIV prevention materials during the past 12 months, including condoms (50%) and sterile syringes (44%) and other injection equipment (41%). One third of participants had been in an alcohol or a drug treatment program, and 21% had participated in an individual- or a group-level HIV behavioral intervention. INTERPRETATION: IDUs in the United States continue to engage in sexual and drug-use behaviors that increase their risk for HIV infection. The large percentage of participants in this study who reported engaging in both unprotected sex and receptive sharing of syringes supports the need for HIV prevention programs to address both injection and sex-related risk behaviors among IDUs. Although most participants had been tested for HIV infection previously, less than half had been tested in the past year as recommended by CDC. In addition, many participants had not been vaccinated against hepatitis A and B as recommended by CDC. Although all participants had injected drugs during the past year, only a small percentage had recently participated in an alcohol or a drug treatment program or in a behavioral intervention, suggesting an unmet need for drug treatment and HIV prevention services. PUBLIC HEALTH ACTION: To reduce the number of HIV infections among IDUs, additional efforts are needed to decrease the number of persons who engage in behaviors that increase their risk for HIV infection and to increase their access to HIV testing, alcohol and drug treatment, and other HIV prevention programs. The National HIV/AIDS Strategy for the United States delineates a coordinated response to reduce HIV incidence and HIV-related health disparities among IDUs and other disproportionately affected groups. CDC's high-impact HIV prevention approach provides an essential step toward achieving these goals by using combinations of scientifically proven, cost-effective, and scalable interventions among populations at greatest risk. NHBS data can be used to monitor progress toward the national strategy goals and to guide national and local planning efforts to maximize the impact of HIV prevention programs.