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To describe surgical repair of a large atrial septal defect (ASD) in a cat.Clinical report.A 3-year-old, 3.3 kg, intact male Japanese domestic short-haired cat.A 10.2-mm-diameter ASD detected by echocardiography was surgically corrected because pulmonary vascular resistance-to-systemic vascular resistance ratio (Qp/Qs) was 3.2. Using cardiopulmonary bypass (CPB), open surgical repair was achieved with an expanded polytetrafluoroethylene (e-PTFE) graft. The priming volume of the CPB circuit was minimized by cutting the CPB tubing, and partially replacing the priming fluid with whole cat blood. To prevent hemodilution associated with use of cardioprotective agents, surgery was performed on the beating heart.At 1-year echocardiographic evaluation, the repair was intact, and at 3 years, the cat was alive without need of medication.Large ASD in a cat can be repaired using e-PTFE under CPB.