The purpose of the study was the evaluation of 2-polyhydroxyethyl methacrylate (2-P-HEMA) for endovascular liquid embolization of experimental side-wall aneurysms following stent protection in a canine model. The swelling behaviour and polymerization characteristics of 2-P-HEMA in different solutions were investigated in vitro. Different methods for applications were tested in a latex aneurysm model under pulsatile flow conditions. Twenty broad-based carotid side-wall aneurysms were microsurgically produced in five dogs. Four weeks after surgery self-expandable nitinol stents were placed, covering the orifice of the aneurysms. 2-P-HEMA was injected via a microcatheter, which was positioned through the meshwork of the stent. Control angiography was performed immediately after treatment and after 1, 6 and 9 months. In-vivo stent placement succeeded in all but one case. Two aneurysms occluded spontaneously after stent placement. Combined embolization of 17 aneurysms using a stent and 2-P-HEMA was performed. Eleven aneurysms could be primarily completely occluded (65%). A small remaining neck was evident in six aneurysms. Efflux of 2-P-HEMA during the process of embolization was observed in seven aneurysms, due to an excess volume of 2-P-HEMA. The excessive 2-P-HEMA led to significant vessel stenosis in two cases. Two carotid arteries (three treated aneurysms) occluded after 1 month, due to insufficient anticoagulation management. Histological examination of embolized aneurysms revealed no foreign-body or inflammatory reaction. A smooth neo-intimal layer covered the stented vessel segment. Liquid embolization of side-wall aneurysms with 2-P-HEMA is technically feasible. Embolotherapy of aneurysms with liquid agents still has the risk that embolic material will exit even when it is stent-protected. To avoid this problem, stents with smaller strut diameter and/or additional balloon-protection are required. The inert 2-P-HEMA seems to be a promising agent for combining techniques of aneurysm treatment.