A collagen hemostatic puncture closure device has been developed as an alternative to traditional manual pressure techniques for achieving effective femoral arterial hemostasis after coronary angiography. The purpose of the current study was to determine if patients receiving this device can ambulate safely at 1 hour compared with patients receiving traditional manual pressure and bed rest after sheath removal for diagnostic cardiac catheterization. Patients (n = 304) were randomized to either the device group (n = 202) with ambulation at 1 hour after sheath removal or to the manual pressure control group (n = 102) with ambulation at 4 to 6 hours after sheath removal. The device group achieved earlier time to hemostasis (0.9 +/- 3 vs 17.0 +/- 8 minutes, p = 0.0001) and faster time to outpatient discharge (5.0 +/- 4 vs 7.7 +/- 4 hours, p = 0.0001) compared with the control group. There were bleeding or vascular complications in 19 patients (9%) in the device group and in 6 patients (6%) in the manual pressure group (p = 0.397). In patients undergoing diagnostic coronary angiography, this device, compared with traditional techniques for achieving hemostasis after sheath removal, allows for faster time to effective hemostasis with resultant earlier discharge from the hospital.