Prosthetic valve thrombosis (PVT) defined as any obstruction of prosthesis by noninfective thrombotic material remains a serious and potentially lethal complication. Treatment of PVT includes administration of thrombolytic agents or surgery. Various thrombolytic treatments including streptokinase, urokinase and recombinant tissue plasminogen activators have been reported with variable success rates. However, the data on the use of Tenecteplase (a synthetic tissue plasminogen activator) is limited. We report here a case of 28-year-old male patient, who presented to us with Aortic PVT of 4 weeks duration and successfully treated with i.v bolus Tenecteplase. The patient underwent aortic valve replacement with St. Jude 21 mm mechanical prosthetic valve on 15/2/2007 for severe aortic regurgitation and was on oral anticoagulant (warfarin 5 mg and 7.5 mg on alternate days), maintaining INR in therapeutic range during regular follow up over the last 5 years. He presented on 19/6/2012 with progressively increasing dyspnea of NYHA class II of 1 month duration. It was found that his oral anticoagulant was changed from Warfarin to Acitrom (Nicoumalone) 2 mg daily by another physician inspite of therapeutic INR. Follow up INR measurements are not available after the changeover. Further he stopped oral anticoagulant for 1 week before presentation. On examination he was comfortable at rest, vitals normal, not in heart failure and auscultation revealed decreased intensity of prosthetic valve click and a grade 3/6 midsystolic murmur. 2DECHO revealed decreased mobility of aortic prosthetic leaflet, Aortic maximum velocity was 5.3 m/second, maximum and mean gradients across aortic valve was 113 mmHg and 66 mmHg (Fig. 1). His LVEF was 64%. Fluoroscopy and TEE showed severely restricted aortic leaflet mobility. His INR was 1.38. Fig. 1 Doppler showing high aortic valve gradient before thrombolysis. After discussing various options, we chose to treat him with intravenous Tenecteplase (Metalyse, Boehringer Ingelheim) 40 mg bolus as in acute myocardial infarction regimen, followed by enoxaparin and warfarin. Post thrombolysis, patient subjectively felt improvement within 6 hours, prosthetic valve clicks became sharp, midsystolic murmur decreased to grade 1/6. After 48 hours vitals were stable, click was well audible and murmur disappeared. 2DECHO showed full mobility of aortic leaflets, and aortic valve maximum and mean gradients were decreased to 16 mmHg and 9 mmHg (Fig. 2). Fluoroscopy and TEE demonstrated completely mobile prosthetic aortic leaflets. Patient was discharged home on therapeutic INR of 3.2. Fig. 2 Doppler showing normal aortic valve gradient after successful thrombolysis. PVT has an estimated incidence of 0.03%–4.3% per year1 and is reported to occur in 0.5%–8% of the left-sided prosthetic valves and in up to 20% of tricuspid prostheses. The most common cause of PVT is inadequate anticoagulant therapy (in up to 82% of cases). Optimal management of PVT remains controversial. As per ACC/AHA Guidelines 2008, for left-sided PVT, emergency surgery is indicated in patients with NYHA functional class III–IV (class IIa) and fibrinolytic therapy for patients in functional class I–II (class IIb).2 Lengyel and coworkers consider thrombolysis as the first line treatment for obstructive PVT, independent of NYHA class and thrombus size, if there are no contraindications.3 On the other hand, in a recent series of 210 patients reported by Roudaut, surgical treatment was associated with significantly better long-term results in terms of recurrence and mortality and a lower incidence of embolic complications, which reached 15% in the fibrinolysis group.4 The fibrinolytic agents used for treatment of PVT are streptokinase, urokinase and recombinant tissue plasminogen activator (alteplase). The newer fibrinolytic agent Tenecteplase is a synthetically engineered variant of alteplase designed to have increased fibrin specificity, greater efficacy, increased resistance to plasminogen activator inhibitor-1 (PAI-1) and a longer half-life, ease of administration as a single intravenous bolus dose. It has been used extensively in acute myocardial infarction but there are anecdotal reports of its use in treatment of mitral and Aortic PVT. Charokopos et al were the first to publish report of Tenecteplase for Aortic PVT; the patient was defaulted on oral anticoagulants and presented with PVT on reinitiating oral anticoagulants without heparin cover.5 Our patient was symptomatic since 3 weeks; the thrombus might have started slowly progressing, impinging valve mobility. As Tenecteplase is more fibrin specific and easy to administer, we thought it as better choice in such a longer duration thrombus. In case thrombolysis fails, re-exploration and possible Aortic valve replacement was planned. Recently Sharma et al6 published their experience of 10 patients with left-sided PVT which included one patient with both Mitral and Aortic PVT and one patient with Aortic PVT. PVT may be successfully treated with Tenecteplase. More experience of its use might establish its role as thrombolytic agent of choice in management of PVT. Proper care should be exercised when switching from one oral anticoagulant to another.