The role of non-HLA antibodies following solid organ transplantation is unclear. In patients, antibodies to the autoantigen vimentin are associated with transplant associated coronary artery disease after cardiac transplantation. However, whether these antibodies are directly damaging or a bystander effect is unknown. Here we have investigated survival of cardiac grafts in mice undergoing and an immune response to vimentin. C57BL/6 mice received two subcutaneous injections (7 days apart) of recombinant vimentin in Freunds incomplete adjuvant, controls received urea in saline. Two weeks after the first injection they received heterotopic heart transplants from syngeneic or allogeneic (129/sv) donors. Hearts were palpated every day to estimate graft survival and rejected hearts were subjected to histological and immunocytochemical analysis. Antibodies to vimentin were quantitated by ELISA. Immunised mice (n = 7) produced signficant IgG anti-vimentin titres at two weeks after immunisation (mean titre 516+/−365, compared to controls 5.75+/−6.3, p = 0.001). The survival of syngeneic hearts in saline/urea immunised mice was 100% at 32 days (n = 7) whereas the mean survival time of the syngeneic heart in vimentin immunised mice (n = 7) was 14.1+/−4.3 days (p = 0.0007). Histology of the mice’s own hearts demonstrated no effects of vimentin immunisation. The mean duration of allogeneic grafts in saline immunised and vimentin immunised mice was not different (at 7.4 and 7.0 days respectively). Histology of the rejected hearts showed myocyte necrosis, vascular thrombosis and a mixed cellular infiltrate. Immunocytochemistry showed no T cells in the syngeneic grafts. Immunoglobulin from vimentin immunised but not control mice bound to cultured C57BL/6 mouse endothelial cells treated with hydrogen peroxide (91.7% vs 22.8% ) but not to normal endothelial cells (3.5% vs 3.5%). In conclusion, the results suggest that the autoimmune response to vimentin is potentially damaging and that surgical manipulation maybe sufficient to sensitise the grafts to autoimmune damage.