Calcineurin inhibitors are the cornerstone of solid organ transplant immunosuppression. Tacrolimus has only recently become available in a non-branded formulation, and there is little data on the efficacy and safety of generic tacrolimus, particularly following heart transplant. We performed a retrospective analysis of 21 consecutive patients who were treated with generic tacrolimus following heart transplant and compared rate of biopsy-proven acute cellular rejection to historical controls who were treated with Prograf. No significant difference in biopsy-proven acute cellular rejection was noted between the groups and rates of opportunistic infection and death were comparable. Although limited by the single-center, retrospective design, this preliminary data may be useful to clinicians facing the option of initiating generic tacrolimus following heart transplant.