There have been no data presented on the relative rates of the development of renal stones in those receiving ritonavir-boosted atazanavir (ATZ/r) when compared with other commonly used antiretrovirals (ARVs). We compared the rate of development of renal stones in a cohort of HIV-infected individuals attending the Chelsea and Westminster Hospital Foundation Trust exposed to ATZ/r with those exposed to efavirenz (EFV)/ritonavir-boosted lopinavir (LPV/r) and ritonavir-boosted darunavir (DRV/r) over a 45-month study period. The rate of development of renal stones in the ATZ/r group (n = 1206) compared with the EFV/LPV/r/DRV/r combined group (n = 4449) was 7.3 [95% confidence interval (CI) 4.7-10.8] per 1000 patient-years and 1.9 (95% CI 1.2-2.8) per 1000 patient-years (P < 0.001), respectively. The renal stones rate remained significantly higher in the ATZ/r group after adjusting for prior ATZ/r/indinavir (IND) exposure. When choosing a boosted protease inhibitor, ATZ/r renal stones should be considered as a potential comorbidity.