The aim of the study was to investigate (1) the safety and efficacy of the application of a collagen plug (Vasoseal) at arterial puncture sites, (2) the hemostasis time, and (3) the comfort for the patient of a collagen plug (Vasoseal) when compared with manual compression. Sixty-two patients were randomized either for application of a collagen plug (Vasoseal, group A, n = 33) or manual compression (group B, n = 29) after cardiac catheterization. All patients were evaluated for subjective pain score ranging from 1 to 5 (1 = no pain up to 5 = very strong pain). In addition the authors measured the time until hemostasis could be achieved. The patients were evaluated by duplex sonography for complications at days 1 and 7 after the procedure. The pain score demonstrated a significantly lower score in group A when compared with group B (P = 0.01). The mean time for hemostasis was significantly lower in group A (mean 9.6 minutes) when compared with group B (mean 23.6 minutes) (P = 0.0001). Regarding the complication rate there was no significant difference between the groups (group A vs group B, P = 0.82). The authors conclude that the application of a collagen plug at the arterial puncture site is a safe and time-saving method. In addition it is less painful and therefore better tolerated than manual compression.