Background: Tacrolimus and cyclosporine microemulsion are the 2 major immunosuppressants for heart transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. This meta-analysis of randomized controlled trials compared the beneficial and harmful effects of tacrolimus and microemulsion cyclosporine for heart transplant recipients. Methods: Electronic databases and manual bibliography searches were conducted. A meta-analysis was performed of all randomized controlled trials comparing tacrolimus with cyclosporine microemulsion as primary immunosuppression for heart transplant recipients. Data for mortality, acute rejection, withdrawals, and adverse events were extracted. The combined results of the data of the randomized controlled trials were summarized as relative risk with 95% confidence intervals. Results: The study assessed 7 randomized controlled trials including 885 patients. There was no difference in mortality at 1 year between recipients treated with tacrolimus and cyclosporine microemulsion. Tacrolimus-treated patients had less acute rejection risk at 6 months and 1 year. Fewer patients stopped tacrolimus than cyclosporine microemulsion. The rate of new-onset diabetes mellitus requiring insulin treatment was higher with tacrolimus. More post-transplantation hypertension occurred with cyclosporine microemulsion. The groups had comparable incidences of malignancy and renal failure needing dialysis. Conclusions: The use of tacrolimus as primary immunosuppressant for heart transplant recipients results in comparable survival and a significant reduction in acute rejection compared with cyclosporine microemulsion. Crown Copyright © 2009.