Background: Trans-catheter mitral valve replacement (TMVR) is an exciting alternative therapy for complex patients with mitral valve disease. The experience with TMVR is new and there is a lot yet to discover about their durability, long-term outcomes, and complications including, mitral transcatheter heart valve (THV) thrombosis. Many factors have been speculated to be associated with the increased risk of THV thrombosis. Here, we report a case of mitral THV thrombosis then discuss published data on the subject. Case presentation: A 72-year-old woman who underwent TMVR for severe mitral regurgitation with mitral annular calcification. She was discharged on aspirin and clopidogrel for thromboprophylaxis. She presented after 30 days with symptomatic heart failure. Her transesophageal echocardiogram showed increased mean trans-mitral gradient with severe subvalvular thickening with immobile neo-anterior leaflet. She was subsequently started on a heparin drip with bridge to warfarin with international normalized ratio goal of 2.5 to 3.5. Discussion: Since most patients undergoing TMVR are within a high-risk population, caution should be implemented to minimize complications, valve dysfunction, and failure. We reviewed 42 TMVR papers with total of 1484 patients including 60 with mitral THV thrombosis. We discussed the most common strategies used for mitral THV thromboprophylaxis and treatment. Conclusion: Given current evidence, post-TMVR anticoagulation should be considered for at least 3 months, especially in those without significant bleeding risk. Longer anti-coagulation therapy should be considered for patients with multiple risk factors for thrombus formation. Additionally, systematic active screening with close clinical follow up help promptly identify those with subclinical THV thrombosis or need longer anti-coagulation therapy.