Combined immunosuppression therapy and acute rejection surveillance after heart transplantation may influence clinical outcome. This prospective, longitudinal study investigated 27 pediatric patients (12 days to 12 yr of age; mean 3.0 yr) who underwent a post-operative regimen that included long-term treatment with cyclosporin A and azathioprine (double immunosuppression) and polyclonal anti-thymocyte serum induction therapy. Non-invasive parameters were used to diagnose acute rejection. The actuarial survival, clinical outcomes, and complications were analyzed. The actuarial survival after double immunosuppression and induction therapy with polyclonal anti-thymocyte serum was 89%, 73%, and 57% at 1, 4, and 8 yr, respectively. The rejection frequency was 2.6 episodes/patient and the infection frequency, 3.7 episodes/patient. One year after transplantation, systemic arterial hypertension was detected in 21% of patients. Hence, double immunosuppression with polyclonal anti-thymocyte serum induction therapy combined with surveillance of acute rejection with non-invasive tests may provide promising clinical outcome in pediatric heart transplant recipients.