Objective: Particularly with the transfemoral access, potential complications at the puncture site with early exercise are a major concern. The purpose of this study was to compare femoral artery access site complications after percutaneous coronary interventions (PCI) in 1) patients following a standard care procedure and 2) performing treadmill electrocardiographic (ECG) stress testing within 24 h after application of the Angioseal™ vascular closure device.Methods: This is a prospective, randomised, single-center cohort study conducted in a high-volume tertiary interventional heart centre in Duisburg, Germany. 221 patients were included and 200 entered analysis. Patients were randomly assigned to treadmill testing within 24 h after transfemoral seven French (F) PCI or discharged with the recommendation of limited exercise for two weeks. Clinical examination and Duplex ultrasound (DUS) of the inguinal region was obtained within 24 h after PCI in both groups and repeated immediately after the treadmill test in the exercise group. Two-weeks clinical follow-up was obtained in both groups. Results:Early treadmill testing could be performed without any major limitations or acute complications in all assigned patients. DUS showed no new pseudoaneurysm (PSA) or arteriovenous fistula (AVF) after treadmill testing. At follow-up, there were 1) no differences regarding pain or physical limitations between the two groups and 2) four patients (4%) in the exercise group and seven patients (7%) in the standard care group developed major hematoma (>6 cm)/minor bleeding, which were clinically uneventful. Conclusions:Treadmill ECG stress testing within 24 h of PCI with the femoral access site closed by the Angioseal device was not associated with a higher complication rate compared to standard care.