The influence of preexisting diabetes mellitus (DM) on outcome after orthotopic liver transplantation (OLT) has not been well defined. The objective of our study was to compare the morbidity and mortality after OLT in 57 patients with preexisting DM (3 type I, 54 type II) with 114 age-, sex-, and race-matched patients without DM (case controls). The demographics were similar in both groups. Pretransplantation serum creatinine was significantly higher in the diabetic group compared with case controls. The incidence of the following complications was significantly higher in the diabetic group after OLT: cardiovascular (61.4% vs. 21.9%, P <.001), major (54.4% vs. 29.8%, P =.002) and minor infections (29.8% vs. 7.9%, P <.0001), renal (59.7% vs. 20.2%, P <.001), ophthalmologic (10.5% vs. 0.9%, P =.01), respiratory (24.6% vs. 7.0%, P =.001), neurologic (31.6% vs. 7.0%, P <.001), hematologic (19.3% vss 2.6%, P =.001), musculoskeletal (24.6% vs. 5.3%, P =.001), and malignancy (22.8% vs. 10.5%, P =.03). The duration of hospital stay, cost of hospitalization, retransplantation, and overall graft survival were similar. Acute rejection was seen in 50.9% of diabetics compared with 25.4% in controls (P =.0009). One-year (87% vs. 77%) and 2-year (81.6% vs. 70.1%) patient survival was similar, but 5-year survival was lower in the DM group (34.4% vs. 67.7%, P =.002). In conclusion, preexisting diabetes is associated with a significant post-OLT morbidity and mortality, and our observations suggest that patients with DM warrant more rigorous pre- and post-OLT evaluation.