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Antibody‐mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and the optimal treatment of this condition is poorly defined. Rituximab has been used successfully for the treatment for antibody‐mediated diseases; however, its role in AMR is unclear. We review our experience with rituximab in patients with cardiac allograft AMR. We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR from 2001 to 2011. Inclusion criteria were clinical suspicion of rejection with the presence of C4d complement staining on endomyocardial biopsy and the absence of cellular rejection of grade 2R or greater. Patients were divided into Rituximab and NoRituximab groups. The primary endpoint was all‐cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and rehospitalization. Thirty‐three patients met inclusion criteria, of whom 13 received rituximab and 20 did not. Baseline characteristics were similar between groups. Kaplan–Meier curves for a three‐yr follow‐up period demonstrate improved survival in the Rituximab group (p = 0.0089). There were no differences in secondary endpoints. We found that rituximab therapy was associated with improved survival in cardiac allograft AMR. Further prospective, randomized studies in larger patient populations are needed to confirm this finding and to define ideal timing for rituximab administration.