BACKGROUND: Isolated tricuspid valve Libman-Sacks endocarditis (LSE) is extremely rare, and its occurrence during pregnancy with severe thrombocytopenia poses major diagnostic and therapeutic challenges. CASE SUMMARY: A 21-year-old pregnant woman at 13 weeks of gestation with systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) presented with severe thrombocytopenia (platelet count 21 × 109/L). Echocardiography revealed two isolated tricuspid vegetations (the largest measuring 24.1 × 19.3 mm). She declined surgery and insisted on continuing the pregnancy with medical management. Treatment included pulse methylprednisolone, plasma exchange, intravenous immunoglobulin, cyclosporine, hydroxychloroquine, and anticoagulation. Anticoagulation was initiated after partial platelet recovery. The patient responded favorably, with platelet normalization, progressive vegetation regression, and successful delivery of a healthy infant. Echocardiography at nine months showed near-complete regression of the larger vegetation and complete resolution of the smaller one, with normal valve function. CONCLUSION: This case demonstrates that intensive immunomodulatory therapy combined with timely anticoagulation after partial platelet recovery can achieve vegetation regression and avoid cardiac surgery in pregnant patients with SLE/APS and massive isolated tricuspid LSE. To our knowledge, this is the first reported case of non-surgical management of this life-threatening condition.