We analysed the impact of recreational drug use (RDU) on different outcomes in people living with HIV (PLHIV). A multicentre retrospective cohort study was performed with two cohorts of PLHIV included: people using recreational drugs (PURD) vs. people not using recreational drugs (PNURD). Overall, 275 PLHIV were included. RDU was associated with men having sex with men (OR 4.14, 95% CI 1.14, 5.19), previous sexually transmitted infections (OR 4.00, 95% CI 1.97, 8.13), and current smoking (OR 2.74, 95% CI 1.44, 5.19). While the CD 4 /CD 8 ratio increased amongst PNURD during the follow-up year, it decreased amongst PURD ( p  = 0.050). PURD presented lower scores of self-reported and multi-interval antiretroviral adherence ( p  = 0.017, and p  = 0.006, respectively), emotional well-being ( p  < 0.0001), and regular follow-up ( p  = 0.059), but paid more visits to the emergency unit ( p  = 0.046). RDU worsens clinical, immunological, and mental health outcomes amongst PLHIV.