OBJECTIVES: Meta-analyses of randomized controlled trials suggest angiotensin-converting enzyme inhibitors (ACEIs) may reduce the rate of kidney failure compared to angiotensin II receptor blockers (ARBs) among patients with chronic kidney disease (CKD). However, controlled trials have not enrolled enough patients to permit precise inferences for this important population. We examined the comparative effects of ACEIs and ARBs on renal and cardiovascular outcomes among CKD patients using insurance claims data. METHODS: We conducted a retrospective new-user cohort study using national U.S. data from OptumLabs on privately insured individuals and Medicare Advantage enrollees. We identified individuals ≥18 years old with CKD who initiated therapy with an ACEI or ARB between 2005 and 2015 after ≥6 months of nonuse. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by inverse probability of treatment weighting to compare ACEIs versus ARBs for progression to end-stage renal disease (ESRD), myocardial infarction (MI), and ischemic stroke. RESULTS:  The study cohort comprised 48,489 patients, with a total of 3,148 ESRD progression, 1,011 MI, and 741 stroke events. Mean follow-up was 2.2 years. Inverse probability weighting resulted in well-balanced treatment groups. HRs comparing patients treated with ACEIs to those treated with ARBs were 0.87 (95% CI, 0.80-0.94) for ESRD, 1.08 (95% CI, 0.93-1.25) for MI, 1.10 (95% CI 0.93-1.30) for stroke, and 1.10 (95% CI 0.98-1.23) for the composite of stroke or MI. Results were consistent across stability analyses using different outcome definitions, treatment washout periods, and continuous enrollment periods. CONCLUSIONS:  Use of ACEIs among CKD patients was associated with a lower rate of ESRD and similar rates of cardiovascular outcomes compared with use of ARBs. Our results are consistent with the results of meta-analyses of CKD clinical trials, but are more precise, and suggest that ACEIs may be the preferred treatment to slow CKD progression.