Simultaneous liver-kidney transplantation is lifesaving, however, the utility of allocating 2 organs to a single recipient remains controversial, particularly in the face of potentially inferior survival. This study aims to determine the effect of renal indication for transplantation on simultaneous liver-kidney transplantation outcomes. All adult recipients of combined whole liver-kidney transplants in the United Network for Organ Sharing database from 2003 to 2016 with a renal diagnosis of hypertension (HTN), diabetes mellitus (DM), acute tubular necrosis (ATN), or hepatorenal syndrome (HRS) were examined. Comparisons were made between the HTN/DM group and the ATN/HRS group using standard statistical methods. There were 1,204 patients in the HRS/ATN group vs 1,272 patients in the HTN/DM group. The HTN/DM patients were slightly older (58.1 vs 56.4 years; p < 0.001), more likely to have liver disease due to chronic viral hepatitis (33.2% vs 21.5%; p < 0.001), and less acutely ill (mean Model for End-Stage Liver Disease score of 27.2 vs 33.1; p < 0.001) than their HRS/ATN counterparts. The prevalence of nonalcoholic steatohepatitis was 16.8% in both groups. Donor demographics were similar in both groups, although HTN/DM patients were more likely to have a local (81.6% vs 67.7%; p < 0.001) rather than regional donor. Patient survival rates at 1, 3, and 5 years were significantly lower in the HTN/DM group (87.4%, 78.2%, and 71.2% vs 90.7%, 84.1%, and 76.6%, respectively). Median survival was 118 months for the HTN/DM group vs 139.7 months for the HRS/ATN (p < 0.001). The HTN/DM patients were at significantly higher risk of death (hazard ratio 1.533; p < 0.001), liver graft loss (hazard ratio 1.611; p < 0.001), and renal graft loss (hazard ratio 1.592; p < 0.001) than ATN/HRS patients on multivariable analysis. Despite a lower acuity of illness, HTN/DM patients have inferior survival after simultaneous liver-kidney transplantation than those with ATN/HRS. This should be considered in risk adjustment and allocation schemes.