Background A previous randomized controlled trial evaluating the use of spironolactone in head failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure hove changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. Methods We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K+ >5.0 mEq/L) or renal insufficiency (Cr greater than or equal to 2.5 mg/dl), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. Results Sixty-seven of 926 patients (7.2%) required discontinuation of spironaloctone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to hove diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with, beta-blockers than controls (n = 134). Patients who developed renal insufficiency hod lower baseline body weight. and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiozide diuretics than controls. Conclusions Spironolactone-induced hyperkalemia and renal insufficiency ore more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.