Background Methamphetamine use has been associated with rising STI/HIV transmission rates, particularly among men who have sex with men (MSM). Interventions which successfully reduce risk for HIV transmission among this population are a public health priority. This study examined the efficacy of a behavioral intervention for increasing safer sex behaviors in the context of ongoing methamphetamine use in a sample of HIV-positive, methamphetamine-using MSM. Methods Three-hundred and forty-one participants from San Diego, CA were randomly assigned to receive either a safer sex behavioral intervention (EDGE) or a time-equivalent diet-and-exercise attention-control condition. Random effects regression analyses were used to evaluate change in safer sex behaviors over a 12-month period. Results Participants in the EDGE intervention engaged in significantly more protected sex acts at the 8-month ( p = 0.034) and 12-month assessment ( p = 0.007). By 12-months post-baseline, a greater percentage of protected sex acts was observed for EDGE (25.8%) vs. control participants (18.7%) ( p = 0.038). There was a significant time-by-intervention interaction ( p = 0.018) for self-efficacy for condom use, suggesting that EDGE participants’ self-efficacy demonstrated a greater increase over time compared to control participants. Conclusions These results suggest that it is possible to reduce high risk sexual behaviors in the context of ongoing methamphetamine use among HIV-infected MSM.