Harm reduction approaches endeavor to assist individuals with avoiding the most detrimental consequences of risk taking behaviors, but limited research has documented the outcomes of harm reduction substance abuse treatment. In total, 211 methamphetamine-using men who have sex with men (MSM) enrolled in two outcome studies of substance abuse treatment programs that were implementing an evidence-based, cognitive-behavioral intervention (i.e., the Matrix Model) from a harm reduction perspective. Study 1 (N = 123) examined changes in self-reported substance use, Addiction Severity Index (ASI) composite scores, and HIV care indicators over a 12-month follow-up. Study 2 (N = 88) assessed changes in substance use, sexual risk taking, and HIV care indicators over a 6-month follow-up. Participants in study 1 reported reductions in cocaine/crack use as well as decreases in the ASI drug and employment composite scores. Among HIV-positive participants in study 1 (n = 75), 47 % initiated or consistently utilized anti-retroviral therapy and this was paralleled by significant increases in self-reported undetectable HIV viral load. Study 2 participants reported reductions in methamphetamine use, erectile dysfunction medication use in combination with other substances, and sexual risk-taking behavior while using methamphetamine. Participants in both studies reported concurrent increases in marijuana use. Taken together, these studies are among the first to observe that clients may reduce stimulant use and concomitant sexual risk-taking behavior during harm reduction substance abuse treatment. Randomized controlled trials are needed to examine the differential effectiveness of harm reduction and abstinence-based approaches to substance abuse treatment.