Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes. To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease. This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone. Renal function and adverse renal events were compared between the CPAP (n = 102) and usual care (n = 98) groups. Glomerular filtration rate was estimated at randomization and at the end of follow-up, and the urinary albumin-to-creatinine ratio was measured at study exit. In 200 substudy participants (mean age, 64 yr; median, 4% oxygen desaturation index; 20 events/h; mean estimated glomerular filtration rate at baseline, 82 ml/min/1.73 m ), the median (interquartile range) changes in estimated glomerular filtration rate (ml/min/1.73 m /yr) were -1.64 (-3.45 to -0.740) in the CPAP group and -2.30 (-4.53 to -0.71) in the usual care group (P = 0.21) after a median of 4.4 years. There were no between-group differences in end-of-study urinary albumin-to-creatinine ratio or in the occurrence of serious renal or urinary adverse events during the trial. The level of CPAP adherence did not influence the findings. CPAP treatment of OSA in patients with cardiovascular disease does not alter renal function or the occurrence of renal adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT00738179).