A pilot study was carried out to prospectively evaluate the efficacy and safety of Tenecteplase (TNKase) using a modified ’lyse and wait” technique with percutaneous transluminal angioplasty (PTA) to treat thrombosed hemodialysis arteriovenous grafts (AVG)s. Seven patients with eight hemodialysis AVGs were treated and followed up to 1 year. Dosing included 1 mg TNKase and 3,000–4,000 U of heparin. Technical and clinical success rates were 100% and 88%, respectively. No major complications occurred. Primary patency rates at 30, 90, and 180 days were 62%, 50%, and 33%, respectively. TNKase, used in this fashion, may be comparable to alteplase and reteplase for safe and effective thrombolysis of PTFE dialysis grafts.