Methamphetamine use, which has been linked to unprotected anal intercourse and incident HIV infection, is an important contributor to HIV transmission among men who have sex with men (MSM). The purpose of this study was to develop and pilot test a single-session motivational interviewing (MI) intervention for reducing HIV risk among an out-of-treatment sample of MSM who use methamphetamine. MSM who use methamphetamine (n = 39) were recruited in 2008 and 2009 in North Carolina. They completed baseline data collection and a single-session MI intervention. Eighty percent completed a follow-up interview two months after enrollment. Men reported reductions in methamphetamine use during the previous 60 days from an average of 9.4 days at baseline to 3.3 days at follow-up (p < 0.05) and unprotected anal intercourse from an average of 4.8 sex partners during the previous 60 days at baseline to 2.9 at follow-up (p < 0.05). Self-reported unprotected anal intercourse at last sex with a nonprimary partner decreased significantly (from 81% at baseline to 25% at follow-up; p = 0.001). These results suggest that a single-session MI intervention may be useful for reducing methamphetamine use and sexual risk among MSM who use methamphetamine, especially in settings where multisession interventions are not feasible.