The metabolic syndrome (MS) has been implicated as an important nonimmunologic risk factor for chronic renal transplant dysfunction. The aim of this study was to determine the impact of the MS on outcomes in simultaneous kidney-pancreas transplantation (SKPT). Data were available on 241 patients enrolled in a prospective, multicenter randomized study of daclizumab compared with no antibody induction in SKPT. Presence of MS before and after SKPT was defined using NCEP-ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria. Body mass index (BMI) was used as a surrogate for waist circumference. MS was present in 59% of patients pretransplantation but only in 19% of patients 1 year after SKPT (P < .0001). Demographic and transplant characteristics were well matched for those with MS (MS+) and without MS (MS-) at 1 year. Presence of MS at 1 year was associated with the following changes at 3 years: increased serum creatinine level (1.65 mg/dL MS- vs 2.05 mg/dL MS+; P = .13); decreased modification of diet in renal disease calculated glomerular filtration rate (GFR; 58 mL/min MS- vs 48 mL/min MS+; P = .02); increased HgbA1C level (5.6% MS- vs 6.6% MS+; P < .001); and lower pancreas graft (PG) survival rate (88% MS- vs 71% MS+; P = .01). Linear regression analysis identified MS+ and the subgroup of MS+ without functioning PG at 1 year as independent risk factors for renal dysfunction, whereas MS+ with functioning PG at 1 year was not a risk factor for renal dysfunction. Presence of MS at 1 year is associated with long-term renal dysfunction after SKPT. Efforts to decrease early PG failure may help mitigate against MS-associated renal dysfunction.