Peritoneal dialysis is often the renal replacement therapy of choice in pediatric patients, but the smaller catheters are at high risk for occlusion by fibrin clots. Tissue-type plasminogen activator (t-PA) is a recombinant protease specific for fibrin, and has been shown to be an effective thrombolytic for central venous catheters. The present study aimed to demonstrate the effectiveness of t-PA for thrombolysis in occluded peritoneal catheters. Six patients between 3 weeks and 15 years of age presented with 7 episodes of occluded peritoneal catheters. In all cases, t-PA (2 mg in 40 mL normal saline) was instilled into the catheter. Patency was assessed after 60 minutes by rapid instillation and drainage of 10 mL dialysis solution per kilogram patient body weight. Thrombolysis was effective in 4 of 7 attempts. In 2 cases, occlusion occurred in the setting of acute peritonitis. In 2 cases, catheters required surgical replacement. One child developed a leak at the catheter exit site within 24 hours after treatment. No intraperitoneal bleeding was observed, and no changes were observed in systemic coagulation indices [prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), and fibrinogen] assessed pre- and post-thrombolysis. In cases of occluded PD catheters, t-PA appears to be an effective and safe treatment.