Local complications at the radial access site are not frequent, hence its large diffusion as the preferred access route for endovascular procedures. However, in a time of fast widespreading, better comprehension of all potential complications becomes critical to facilitate their early recognition and the most appropriate treatment. In this case report, we present for the first time a case of sudden massive bleeding at the left wrist, due to spontaneous gross rupture of the left radial artery bleeding 15 days after an endovascular procedure through a left radial arterial access. The patient had been readmitted to the hospital after evidence of local infection at the left wrist with loss of substance. The radial artery was patent with no evidence of pseudoaneurysm. After sudden radial artery rupture, with massive bleeding and suspicion that the local infection could have reached the arterial wall, surgical hemostasis with artery ligation was obtained. Healing of the large wound was then efficiently speeded up using a negative pressure wound therapy. This is the first case of macroscopic radial artery rupture associated with local wrist infection after arterial catheterization. After prompt surgical hemostasis, negative pressure wound therapy was very helpful in favoring healing of the large and deep wound.