Congestive heart failure (CHF) is frequent in patients with chronic renal failure, and may contribute to high cardiovascular morbidity and mortality. There is little data in the literature about the safety and efficacy of use of spironolactone in patients with end-stage renal disease with heart failure. In this study, we evaluated the safety and efficacy of spironolactone in patients on continuous ambulatory peritoneal dialysis (CAPD) with CHF. This randomized prospective double-blind placebo-controlled clinical trial was performed at the St. Al-Zahra peritoneal dialysis center. Eighteen CAPD patients with New York Heart Association (NYHA) class III or IV heart failure, ejection fraction (EF) ≤45%, serum potassium level ≤5.5 mEq/L and who were eligible, were randomly assigned to taking either spironolactone (25 mg every other day) or placebo for six months. The serum potassium was measured monthly and echocardiography was repeated at the end of the study period. The serum potassium levels rose in both groups, and there was no statistically significant difference intragroup and between the groups during the study period. Only in one patient in the spironolactone group did the serum potassium level reach above the critical level (5.70 mEq/L) at the end of the second month of study, necessitating patient exclusion. The EF did not change significantly in the placebo group (33.3 ± 11.7 vs. 34.2 ± 11.6, F = 1, P = 0.363), but in the spironolactone group the EF rose significantly (25.7 ± 7.3 vs. 33.3 ± 7.8, F = 27.45, P = 0.002). Our study suggests that spironolactone could be used in CHF patients on CAPD to improve their cardiac function, but close monitoring of their serum potassium level is required.