The purpose of this study was to examine the efficacy and tolerability of ezetimibe in cardiac transplant recipients who were intolerant of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) or unable to reach target lipid levels with statin therapy. After treatment with ezetimibe (n = 16), mean total and low-density lipoprotein cholesterol levels decreased significantly (228 +/- 40 mg/dl to 197 +/- 48 mg/dl, p = 0.003; and 149 +/- 34 mg/dl to 117 +/- 39 mg/dl, p < 0.001, respectively). One patient required a reduction in ezetimibe dose owing to myalgias; no other adverse events occurred. This initial experience indicates that ezetimibe is well tolerated in cardiac transplant recipients and is effective in reducing total and low-density lipoprotein cholesterol levels.