BACKGROUND.: Left ventricular hypertrophy (LVH) and diastolic dysfunction occur after cardiac transplantation. We investigated sirolimus (SRL) as primary immunosuppression for the attenuation of LVH and diastolic dysfunction of the cardiac allograft. METHODS.: Seventy cardiac transplant recipients were converted to SRL, 5.79±3.90 years after transplant, with complete calcineurin-inhibitor (CNI) withdrawal. Three consecutive echocardiographic studies, 1 year apart, were analyzed for changes in left ventricular (LV) mass and diastolic function during CNI and SRL treatment. RESULTS.: Changes in systolic (P=0.69) and diastolic blood pressures (BP) (P=0.32) did not differ between SRL and CNI treatment. LV mass and LV mass index increased (185.03±41.59-197.21±47.39 g, P=0.033 and 94.20±18.64-98. 93±20.08 g/m; P=0.030) during CNI and decreased (197.21±47.39-187. 59±48.88 g, P=0.025 and 98.93±20.08-94.06±20.31 g/m P=0.050) during SRL. The difference in ΔLV mass and ΔLV mass index was significant (P=0.011 and P=0.017, respectively) and was not associated with changes in BP. Left atrium volume index increased during CNI (46.73±16.3 5-54.20±18.47 cm/m, P=0.006) and decreased during SRL (54.20±18.47-49.75±18.40 cm/m, P=0.0036). The difference in left atrium (ΔLA) volume index was significant (P=0.002) and was not associated with changes in BP. CONCLUSIONS.: Withdrawal of CNI and replacement with SRL in cardiac transplant recipients results in a decrease in LV mass and improvement in diastolic function. SRL may be useful to attenuate LVH and improve cardiac allograft diastolic function. © 2008 by Lippincott Williams and Wilkins.