Introduction:  The influence of gender on outcomes following simultaneous pancreas-kidney transplantation (SPKT) in the new millennium is uncertain.  
Methods:  We retrospectively studied 255 consecutive patients undergoing SPKT from 11/2001 to 8/2020.  Cases were stratified according to donor (D) gender, recipient (R) gender, 4 D/R gender categories, and D/R gender-matched vs mismatched. 
Results:  A total of 170 donors were male and 85 were female.  Male donors were younger, had a lower kidney donor profile index (KDPI), were more commonly non-Caucasian, weighed more and were taller, and more frequently sustained brain death secondary to head trauma compared to female donors (all p<0.05).  The incidences of early pancreas graft loss secondary to thrombosis (5.9%) and early relaparotomy (32.9%) were identical according to donor gender.  There were no differences in patient or pancreas survival rates (GSRs) according to donor gender.  However, the kidney GSR was significantly higher with male donors. 
   
A total of 142 recipients were male and 113 were female. There were no significant survival differences according to recipient gender but female recipients did experience slightly higher pancreas thrombosis (8% R-female vs 4.2% R-male, p=0.28) and early relaparotomy rates (38% R-female vs 29% R-male, p=0.14) compared to male recipients. When analyzing the 4 D/R gender categories, there were no differences in patient or pancreas GSRs.  Early relaparotomy (40.5% vs 31.7%, p=0.34) and pancreas thrombosis (10.8% vs 5.0%, p=0.25) rates were numerically higher in the female/female group compared to the other three D/R groups combined.  The two D-male groups had higher kidney GSRs (83%) compared to the two D-female groups (72%, p=0.02) irrespective of recipient gender.  
   
There were no significant differences in outcomes between gender-matched (n=131) and gender-mismatched (n=124) groups although overall survival outcomes were slightly lower with female donors irrespective of recipient gender.  In multivariate analysis, no significant differences were noted in patient or pancreas GSRs according to donor or recipient gender whereas kidney graft loss was influenced by female donors (HR 2.12, p=0.005).
Conclusions:  The influence of D/R gender following SPKT is subject to multiple confounding factors but kidney GSRs appear to be higher in D-male/R-male and lower in D-female/R-female categories.