We investigated tolerability and efficacy of ezetimibe treatment (10 mg/d) in 25 heart allograft recipients already on stable statin therapy. Total cholesterol (TC), low‐density cholesterol (LDL‐C), high‐density cholesterol (HDL‐C), triglycerides (TG), immunosuppressant drug levels, laboratory and clinical parameters were assessed before, four months and one yr after initiation of ezetimibe treatment. Mean equivalent statin dose was 53.5 ± 12.3 mg of pravastatin, remaining unchanged throughout the study period. Ezetimibe was generally well tolerated, only two patients (8%) discontinued ezetimibe due to stomach pain or headache. Mean TC decreased from 231.8 ± 6.4 mg/dL before therapy to 202.2 ± 8.8 mg/dL after four months and 192.9 ± 7.0 mg/dL after one yr (p < 0.001). Mean LDL‐C decreased from 143.1 ± 5.4 mg/dL to 121.4 ± 7.9 mg/dL (month 4; p < 0.05) and 107.1 ± 5.6 mg/dL (one yr; p < 0.001). TG decreased from 182 ± 14.3 mg/dL to 173.3 ± 17.5 mg/dL after one yr (p < 0.05), whereas HDL‐C was unchanged. Initial LDL‐C and cardiac diagnosis before transplantation were identified as predictors of absolute LDL‐C reduction. Immunosuppressant drug doses and blood concentrations were unchanged as well as other laboratory and clinical parameters. Ezetimibe appears safe and effective for further reduction of TC and LDL‐C in heart allograft recipients already on stable statin therapy. Extent of pre‐treatment LDL‐C and cardiac disorder prior to transplantation appear to correlate with the efficacy of ezetimibe therapy.