Immunosuppressive therapy for solid organ transplantation has significantly evolved over the past decade. While these therapies have been found to be beneficial in abdominal organ transplantation, the efficacy of these therapies remains unclear in lung transplantation. We retrospectively compared three potent immunosuppressive regimens in our lung transplant population: Group 1 (tacrolimus/azathioprine/prednisone), Group 2 (tacrolimus/azathioprine/prednisone/daclizumab) and Group 3 (tacrolimus/mycophenolate mofetil/prednisone/daclizumab). We compared these three groups with respect to 3-year rates of acute rejection, chronic rejection, infection and survival. A total of 109 patients was followed during the course of this study. There were 32 patients in Group 1, 49 patients in Group 2 and 28 patients in Group 3. Freedom from acute rejection at 1 and 3 years were higher in Group 3 compared with Group 1 (p < 0.05). The overall incidence of infection up to 3 years after transplantation was comparable among all three groups. Freedom from chronic rejection and survival at 1 and 3 years did not differ among the three groups. In conclusion, we determined the safety and efficacy of three potent immunosuppressive regimens in lung transplantation. Addition of daclizumab and MMF to a tacrolimus-based immunosuppressive regimen decreased the incidence of acute rejection episodes without increasing any adverse events in our lung transplantation population.