Background: The prosthetic heart valve thrombosis (PVT) is a life-threatening complication of mechanical valve prosthesis. It can be attributed more frequently to inadequate anticoagulant therapy. In the aortic and mitral position, reported incidences vary widely from 0.5% to 6% per patient-year, and are highest in the mitral position and up to 20% in tricuspid valve prosthesis. Medical therapy (Thrombolysis) has emerged as an alternative therapy in high-risk surgical patients, considering that surgical prosthetic valve replacement is related to significant operative morbidity and mortality rates. The purpose of this study is to present a single-center experience of 205 consecutive patients hospitalized between 2000 and 2016. Methods: From 2000 to 2016, 205 consecutive patients were hospitalized in our center for mechanical prosthetic valve thrombosis (PVT). The diagnosis of PVT was mainly assessed by echocardiography and/or fluoroscopy. There were 41 men and 164 women aged between 07 to 75 years. Prosthetic valve location was mitral in 191 patients, tricuspid in 05, aortic in 8 and mitro-tricuspid in one case. Predisposing causes of MVT were: poor compliance with warfarin, pregnancy or unknown. The interval from first operation to valve thrombosis was from 1 day to 38 years. Delay from first symptoms to hospitalization ranged from 1 to 4 months. The diagnosis was an incidental finding during an echocardiography, on the basis of a subacute increase in the transvalvular mean gradient seen due to thrombotic obstruction on transthoracic echocardiography and was confirmed by transesophageal echocardiography. First clinical symptoms were reported as systemic emboli, progressive exertional dyspnea (NYHA II to III–IV), muffled opening or closing sounds of the prosthetic valve, left heart failure, stroke, and cardiogenic shock. Transthoracic echocardiography is the diagnostic tool often used to evaluate a patient with valve prosthesis, when there is suspicion of PVT, and also is useful in the follow-up of patients during thrombolysis. Fluoroscopy was complementary. Anticoagulation regimen was inadequate, recently stopped or incorrectly conducted. Results: There were two groups, the first group (A) comprised of 135 patients have been operated with cardiopulmonary bypass (CPB) (prosthetic replacement or declotting and excision of pannus). It is an emergency surgery in 101 patients. In this group, we deplore 18 (13.5%). 70 patients underwent medical treatment (heparin, oral anticoagulants and aspirin) on clinical, sonographic and under strict supervision in a hospital and some external purposes for a period of 07 days at 6 months. For the non-operated group, all patients have unlocked their prothesis; we deplored 05 deaths (7.14%) (hemorrhagic stroke, left and right ventricle dysfunction). Conclusion: PVT remains a serious complication of mechanical heart valve prosthetic with high morbidity and mortality despite aggressive treatment by thrombolysis and/or surgery. Surgery treatment should be the preferred therapeutic modality for most patients with PVT. Thrombolysis, followed by heparin, warfarin, and aspirin is advised for high-risk surgical candidates without hemodynamic instability under strict echocardiographic survey. Because of the high risk of thromboembolism during thrombolysis for left sided PVT. For certain category of patients, medical therapy (thrombolysis anticoagulation++aspirin) may be offered in highrisk surgical patients, this with the consent of patients on medical and surgical rigorous monitoring and evaluating the operational risk compared to the risk of progression under medical treatment.