The effectiveness of the Real Men Are Safe (REMAS) HIV prevention intervention was examined as a function of treatment program modality. REMAS was associated with significantly larger decreases in unprotected sexual occasions than an HIV education control condition in both treatment modalities. REMAS had superior effectiveness for reducing unprotected sexual occasions in the psychosocial outpatient compared to methadone. At the 6-month follow-up, the adjusted mean change for REMAS completers in psychosocial outpatient (M=6.4, d=0.38) was greater than for REMAS completers in methadone programs (M=2.3, d=0.25). Reasons for why REMAS appears to be especially effective in psychosocial outpatient programs are explored.