The Randomized Aldactone Evaluation Study (RALES) showed that spironolactone reduces mortality in patients with severe heart failure; however, the drug can cause hyperkalemia, especially when given with angiotensin-converting–enzyme (ACE) inhibitors. The current study found that, after the publication of RALES, there was an abrupt increase in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality in patients with heart failure who were receiving an ACE inhibitor. The Randomized Aldactone Evaluation Study (RALES) showed reduced mortality in patients with severe heart failure. After its publication, there was an increase in hyperkalemia-associated morbidity and mortality. Heart failure affects approximately 5 million persons annually in Canada and the United States. 1 Medications are the mainstay of therapy, and in the past two decades there has been a shift away from the use of diuretics and cardiac glycosides and toward neurohumoral manipulation with angiotensin-converting–enzyme (ACE) inhibitors, beta-adrenergic antagonists, and aldosterone antagonists. 1 Published in September 1999, the Randomized Aldactone Evaluation Study (RALES) demonstrated that treatment with spironolactone substantially reduced morbidity and mortality in patients with severe heart failure. 2 Spironolactone is inexpensive and generally well tolerated, but in these patients it can provoke life-threatening hyperkalemia when combined with ACE inhibitors. . . .