Activation of the renin-angiotensin system (RAS) followed by increased inflammatory cytokines may be important in the pathogenesis of chronic allograft dysfunction. As many renal transplant recipients show chronic changes on biopsy within the first year, early RAS blockade with angiotensin converting enzyme inhibitor (ACEI) could be beneficial. However, it remains unclear that early ACEI use is safe. We conducted a prospective, randomized, placebo-controlled trial to assess the safety of enalapril 5 mg during the early post-transplant period. Subjects took the study medication for six months. Primary endpoints were serum potassium (K) >5.9 mEq/L and 30% increase in baseline creatinine. A total of 53 subjects were randomized, and of them, 27 received the study drug. Twenty-nine subjects, 14 ACEI and 15 controls, completed the six-month protocol without reaching an endpoint. Patients on ACEI had higher K and higher BUN at six months. Serum creatinine, hematocrit, and urinary protein were not different. There was no difference in urinary TGF-β1. Twenty-four subjects reached study endpoints. When the common clinical endpoints of elevated creatinine and hyperkalemia were combined, ACEI group had significantly increased endpoints vs. control (10/13, 77% vs. 5/11, 45%, p < 0.05). We conclude that ACEI use in the early post-transplant period can be safe but patients must be carefully selected and monitored for elevations in serum creatinine and potassium. Whether early ACEI is beneficial in preserving allograft function requires further study. © 2010 John Wiley & Sons A/S.