Objetive. To describe the histopathological characteristics of explanted hearts and post-transplant biopsy specimens at a national reference center in Peru. Materials and Methods. A case series study of patients who underwent heart transplantation between March 2010 and February 2018. Results. Sixty-one (61) transplanted patients with a mean age of 40.1 years (range: 9-66 years). Five cases (8.2%) initially diagnosed as dilated cardiomyopathy were reclassified after the histopathological study. The three leading causes of primary disease after transplantation were: idiopathic dilated cardiomyopathy (50.8%), ischemic cardiomyopathy (16.4%), and valvular cardiomyopathy (6.6%). The mean follow-up was 2.8 years. The post-transplant survival rate was 85.1% at 1 year and 82.8% at 5 years. Moderate/severe acute cellular rejection occurred in 12 patients (21.1%) and antibody-mediated rejection occurred in 3 patients (5.3%). Conclusions. Routine histopathological evaluation of the explanted heart is essential to confirm the etiology of heart failure, especially in cases clinically diagnosed as dilated cardiomyopathy. In addition, routine follow-up through endomyocardial biopsies shows that acute cellular rejection is still a frequent complication after a heart transplant, especially within the first year, and that antibody-mediated rejection has a low incidence in our population.