BACKGROUND: Persons living with HIV (PLWH) who also use crack cocaine may have stressful, chaotic lives and typically do not engage in standard medical care that addresses a multitude of extenuating life circumstances. Yoga/meditation (YM) improves quality of life (QOL) and biomarkers of stress, but the effect of this intervention is almost unknown in PLWH, particularly those who use crack cocaine. OBJECTIVES: This pilot study sought to compare the feasibility and acceptability of 60-minute, twice-per-week sessions of YM for 2 months with those of no-contact control and to evaluate the effects of the intervention on QOL (according to the Short Form-36, Perceived Stress Scale [PSS], and Impact of Events Scale [IES]) and salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) among PLWH who use crack cocaine. DESIGN: Participants were randomly assigned to YM or no-contact control and were assessed at baseline, 2 months after the intervention, and 4 months' follow-up. RESULTS: The YM program was acceptable and feasible, with high overall attendance (89%) and individual participation in yoga sessions (83%). YM participants showed modest improvements on QOL. The PSS total score and the IES intrusion score improved significantly 2 months after the intervention, but cortisol and DHEA-S did not change. CONCLUSIONS: This pilot study showed a high level of feasibility and acceptability and modest effects on measures of QOL among PLWH who use crack cocaine. The results suggest utility of YM as a simple, safe, and inexpensive format to improve QOL in a population that has many medical difficulties and extenuating stressors.