Given ethical concerns about research involving people who inject drugs and those affected by HIV, identifying potential participation benefits is important. We evaluated participant-reported benefits in a trial conducted in Indonesia, Ukraine, and Vietnam that assessed an intervention combining psychosocial counseling and referral for antiretroviral therapy and substance use treatment for HIV-infected people who use drugs. Reported benefits were aggregated into three groups: clinical (antiretroviral therapy, reduced cravings, reduced drug use, lab testing, medical referral, mental health, physical health), social (employment, financial, relationships, reduced stigma), and general (gained knowledge, life improvement). Overall, 438 index participants (90.5%) and 642 injection partners (83.1%) reported at least one benefit. Significantly more index participants who received the study intervention reported at least one benefit versus those who received the standard of care. Clinical trial participation can provide broad direct and indirect benefits for stigmatized populations, which has implications for assessing the ethical appropriateness of studies with such populations.