This study evaluated the safety and efficacy of alteplase in catheter-directed treatment for peripheral arterial and venous thrombosis and considered the optimal dosing regimen. Forty-four patients (49 encounters) underwent transcatheter therapy using alteplase between January and November 1999. The most common indications for thrombolysis were peripheral arterial occlusion (PAO) and venous thrombosis (38 patients, 43 encounters). Each encounter was reviewed for indication, dosage of alteplase, duration of infusion, concomitant use of anticoagulation, degree of lysis, and complications. Patients were divided into low-dose (0.5 to 1.0 mg/hr), mid-dose (1.0 to 1.5 mg/hr), and high-dose (>1.5 mg/hr) groups. For PAO, there was no significant difference in the success rate between the 3 dose groups. A lower complication rate was achieved in the low-dose group. For venous thrombosis, there was no difference in the overall success or complication rates for each of the 3 groups. Partial lysis was achieved more readily in the mid and high-dose groups, but the risk of serious complications was greater. Overall, the complete thrombolysis rate was 71% for PAO and 55% for venous thrombosis. Major and minor complication rates were 7% and 19%, respectively. An equivalent success rate with a lower complication rate can be achieved using a low-dose constant catheter-directed infusion of alteplase for cases of PAO. Cases of venous thrombosis had a lower overall success rate compared with PAO. A mid-dose infusion of alteplase can achieve greater complete and partial thrombolysis rates without increasing the complication rate. Major and minor complication rates were similar to the rates given in the published literature.