Introduction: Vein grafts are used to bypass atherosclerotic lesions; however, patency rates are poor due to the development of vein graft failure. Epidemiologic data shows that low levels of natural anti-phosphorylcholine (anti-PC) antibodies are associated with decreased vein graft patency. We hypothesized that humanized anti-PC IgG monoclonal antibodies are protective for vein graft failure. Methods and results: In vitro studies showed that the monoclonal anti-PC IgG antibodies specifically bound phosphorylcholine and apoptotic cells. Hypercholesterolemic male ApoE3Leiden mice underwent vein graft surgery, by means of interpositioning of a donor caval vein in the carotid artery of a receiver mouse. The mice were treated with weekly intraperitoneal injections of 5 mg/kg anti-PC (n=11) or vehicle (n=12) until sacrifice at 28 days. Anti-PC treatment did not affect plasma cholesterol levels and plasma CCL2 levels. Interestingly, a 32% decrease in vein graft lesion area was observed. Studying the lesion composition revealed no differences in the relative percentage of collagen, smooth muscle cells and macrophages between the anti-PC and vehicle group. Anti-PC however, prevented macrophage oxLDL-uptake and reduced CCL2 production by macrophages in an in vitro setting. Conclusions: The newly synthesized humanized anti-PC IgG monoclonal antibodies are effective inhibitors of vein graft remodeling and hold promise as new therapeutic approach to prevent vein graft disease