OBJECTIVE The authors determined the impact of a positive cytotoxic crossmatch on the outcome of liver transplantation. BACKGROUND Liver allografts rarely undergo hyperacute rejection, but transplants performed across a positive cytotoxic crossmatch tend to follow a different clinical course, with higher intraoperative blood use, postoperative graft dysfunction, and, in some cases, graft loss. How this affects overall graft survival has not been determined. METHODS The authors provide a retrospective analysis of 1520 liver transplants performed between November 1989 and December 1993, with a minimum follow-up of 1 year. All cases had a cytotoxic crossmatch using serum pretreated with dithiothreitol. RESULTS There were 1390 negative crossmatch and 130 positive crossmatch cases. There was no difference in overall graft survival, although early survival rates were lower in the positive crossmatch group, with the maximum difference at 6 months: 0.76 (95% confidence interval, 0.74-0.78) for a negative crossmatch versus 0.68 (95% confidence interval, 0.61-0.77) for a positive crossmatch. These differences become negligible by the 2-year mark. Using stepwise logistic regression, the authors identified seven variables independently associated with outcome: 1) donor age, 2) donor gender, 3) prior liver transplant, 4) medical urgency status, 5) ischemia time, 6) indication for transplantation, and 7) primary immunosuppressant. CONCLUSIONS The cytotoxic crossmatch is not statistically associated with overall graft survival after liver transplantation. However, early failure rates are higher in the positive crossmatch cases, a difference that disappears by the second year.