Copyright © 2014 by Lippincott Williams & Wilkins. Background: HIV-positive persons who use stimulants (eg, methamphetamine) experience profound health disparities, but it remains unclear whether these persist after highly active antiretroviral therapy (HAART) initiation. Conducted within the Multicenter AIDS Cohort Study, this investigation examined whether stimulant use is associated with progression to AIDS or all-cause mortality after the initiation of HAART. Methods: Using marginal structural modeling, the cumulative proportion of visits where any stimulant use was reported (ie, 0%, 1%-49%, 50%-99%, and 100%) was examined as a time-varying predictor of (1) all-cause mortality and (2) AIDS or all-cause mortality. Results: Among the 1313 men who have sex with men (MSM) who initiated HAART, findings showed no significant association of any level of stimulant use with all-cause mortality. A competing risk analysis indicated that no level of stimulant use was associated with increased AIDS-related or non-AIDS mortality separately. Among the 648 participants without AIDS at HAART initiation, a secondary analysis indicated that stimulant use at 50% or more of study visits was associated with a 1.5-fold increase in the odds of progression to AIDS or all-cause mortality (adjusted odds ratio = 1.54; 95% confidence interval: 1.02 to 2.33; P < 0.05). Conclusions: HIV-positive stimulant-using MSM receiving HAART seem to face no greater overall risks for all-cause, AIDS-related, or non-AIDS mortality compared with nonusers. However, men without AIDS at HAART initiation who more frequently reported stimulant use demonstrated modestly increased odds of progression to AIDS or all-cause mortality. Comprehensive approaches are needed to optimize the effectiveness of HAART with stimulant-using MSM.