Background: We hypothesized that total orthotopic heart transplantation (TOHT) improves hemodynamics during cellular rejection compared with biatrial transplantation (SOHT). Methods: We reviewed 1942 biopsies from 134 patients (pts) and right heart catheterization data obtained at endomyocardial biopsy. Biopsies that displayed cellular rejection grade 1B as classified according to International Society for Heart and Lung Transplantation (ISHLT) criteria were analyzed. Pts with pacemakers, atrial fibrillation, or β-blocker therapy at the time of biopsy were excluded. Twenty-three pts after TOHT and 38 after SOHT were identified to match these criteria. Results: Demographic data and pretransplant hemodynamics were similar. TOHT pts had a higher mean cardiac index than SOHT recipients (3.3 ± 0.8 vs 2.7 ± 0.5 L/min/m2; P = .002). Right atrial mean pressure was lower after TOHT (8 ± 4 vs 11 ± 4 mm Hg; P = .006). Pulmonary pressures, pulmonary vascular resistance, and heart rate were similar. Conclusions: TOHT offers improved hemodynamics during cellular rejection grade 1B as evidenced by higher cardiac output and index with lower right atrial pressures. Future studies must examine the potential benefits of TOHT during more severe rejection events.