Treatment of prosthetic heart valve thrombosis using intravenous thrombolytics, although an acceptable alternative to surgery, is not complication free, and the literature has a dearth of data on the subject. This study analyzed the results of fibrinolytic treatment (FT) among a single-center group of patients with mechanical pulmonary valve thrombosis. Between 2000 and 2013, 23 consecutive patients with 25 episodes of pulmonary valve thrombosis received FT. The diagnosis of mechanical pulmonary valve thrombosis was established by fluoroscopy and echocardiography. Streptokinase (SK) was used in 24 cases and alteplase in 1 case. The FT was continued a second day for 14 patients (58.3%), a third day for 1 patient, and a fourth day for 1 patient. Echocardiography and fluoroscopy were performed every day until improvement of malfunction was achieved. Of the 23 patients, 19 had complete resolution of hemodynamic abnormalities after FT, 1 had partial resolution, and 2 showed no change. No patient had major complications. Five minor complications were detected, namely, fever, nausea, thrombophlebitis, epistaxi, and pain. Seven patients (30%) experienced recurrence of thrombosis, whereas four patients had surgery (biological pulmonary valve replacement) without re-thrombolytic therapy, one patient was treated with Alteplase, one patient received SK, and one patient received intense anticoagulation using heparin and warfarin. Overall, FT had a success rate of 84%. The results indicate that regardless of the time to pulmonary valve replacement and echocardiographic and fluoroscopic findings, FT was effective in most cases of mechanical pulmonary valve thrombosis. The efficacy increased with second-day thrombolytic therapy. Major complications were not common after lytic therapy for mechanical pulmonary valve thrombosis.