Until now, no mechanical closure devices were available to achieve fast and secure hemostasis for vessel closure after catheterization of small arterial vessels. Eighty patients were randomized to evaluate the effect on hemostasis by use of a chitosan pad (Chito-Seal, Abbott Vascular Devices, Galway/Ireland) in comparison to manual compression after diagnostic transbrachial arterial catheterization. Hemostasis after three minutes and one hour as well as local development of a hematoma after one and twenty-four hours were assessed. The use of chitosan pads significantly decreased the bleeding time in the first three minutes after manual compression time (p < 0.01). Significant decrease in bleeding risk at three minutes by use of the chitosan closure pads was also found in subgroups of patients with hypertension (p < 0.001) or diabetes (p < 0.01) and also in patients under anticoagulation therapy (p < 0.01). In addition, long-term protection from bleeding complications such as the risk of hematoma was decreased by the use of chitosan closure pads one hour (p < 0.01) or twenty-four hours (p < 0.001) after catheter removal. The use of an intravascular anchor or suture system is not safely applicable in these vessels due to the small diameter of the brachial artery. Our results document a significant improvement in hemostasis by using chitosan pads in these cases.