BACKGROUND Gender differences in graft survival has been reported after some types of organ transplantation, but not after pancreas transplantation. This study compares graft survival between women and men after simultaneous pancreas-kidney transplantation (SPK). METHODS All first time SPK (n = 163) transplants (109 M/54 F) performed between 1989 and 2000 at University of Nebraska Medical Center, where data was available, were analyzed for overall graft and patient survival. Graft failure was then subdivided into early (<6 months), and late (>6 months), and compared between women and men. RESULTS The 5-yr pancreas and kidney graft survival rates for all SPK recipients was 86% [95% confidence interval (CI) = 81-92%] and 87% (95% CI = 82-93%), respectively. While overall pancreas graft survival in women was similar to men (p = 0.16), early pancreas graft failure was greater in women than men (p = 0.010) with no one cause for failure predominant. There was no gender difference in late pancreas graft failure or in early, or late kidney graft failure in the same recipients. The gender difference was unexplained by differences in age, immunosuppression, body mass index (BMI), or diabetes duration between women and men. CONCLUSIONS This is the first report of a gender difference in pancreas graft survival after SPK with greater early (<6 months) pancreas graft failure in women than men. With no gender difference in kidney graft failure in the same individuals, gender differences in immune responses are unlikely to be the cause. Multiple variables likely contribute.