OBJECTIVE: To determine if Healthy Choices, a motivational interviewing intervention targeting multiple risk behaviors, improved human immunodeficiency virus (HIV) viral load. DESIGN: A randomized, 2-group repeated measures design with analysis of data from baseline and 6- and 9-month follow-up collected from 2005 to 2007. SETTING: Five US adolescent medicine HIV clinics. PARTICIPANTS: A convenience sample with at least 1 of 3 risk behaviors (nonadherence to HIV medications, substance abuse, and unprotected sex) was enrolled. The sample was aged 16 to 24 years and primarily African American. Of the 205 enrolled, 19 did not complete baseline data collections, for a final sample size of 186. Young people living with HIV were randomized to the intervention plus specialty care (n = 94) or specialty care alone (n = 92). The 3- and 6-month follow-up rates, respectively, were 86% and 82% for the intervention group and 81% and 73% for controls. Intervention Healthy Choices was a 4-session individual clinic-based motivational interviewing intervention delivered during a 10-week period. Motivational interviewing is a method of communication designed to elicit and reinforce intrinsic motivation for change. Outcome Measure Plasma viral load. RESULTS: Youth randomized to Healthy Choices showed a significant decline in viral load at 6 months postintervention compared with youth in the control condition (beta = -0.36, t = -2.15, P = .03), with those prescribed antiretroviral medications showing the lowest viral loads. Differences were no longer significant at 9 months. CONCLUSION: A motivational interviewing intervention targeting multiple risk behaviors resulted in short-term improvements in viral load for youth living with HIV. Trial Registration clinicaltrials.gov Identifier: NCT00103532.