Several case series published after the Randomized Aldactone Evaluation Study (RALES) have focused on the adverse effects of spironolactone when prescribed to participants not in a trial and the appropriateness of these prescribing practices; however, there is a paucity of data on potential benefits in patients not in a trial. Therefore, we examined data from a prospective cohort study of 1,037 patients with heart failure seen at the University of Alberta Heart Function Clinic. Median age was 69 years, 66% were men, 75% had systolic dysfunction, and mean ejection fraction was 33%. Only 40% of the 136 patients prescribed spironolactone had New York Heart Association class III or IV symptoms, and <25% fulfilled all of the RALES eligibility criteria. Mean daily dose of spironolactone was 23.9 mg; 25% of patients had spironolactone withdrawn after initiation, mostly due to increases in potassium and/or creatinine (9%), gynecomastia (5%), or dehydration/hyponatremia (6%). Only 1 of our spironolactone-treated patients developed serum potassium >6 mmol/L. Cox's proportional hazards analysis confirmed the association between use of spironolactone and increased survival rate (relative risk 0.09, 95% confidence interval 0.02 to 0.39), even though 78% of our patients did not fulfill the RALES eligibility criteria. Thus, although the complication rate was higher, the benefits of spironolactone seen in RALES extended to participants not in a trial who were treated with similar doses and followed closely in a clinic specializing in heart failure.