Thiazolidinediones (TZD) are effective agents for the treatment of hyperglycemia, and appear ideal in diabetic patients with progressive or end-stage renal disease because of its predominant hepatic clearance. Troglitazone, the first available TZD for clinical use, was withdrawn due to safety concerns; however, studies completed with this agent can provide a better understanding of the class effect of TZDs. This study was an open-label, controlled clinical trial examining the safety and efficacy of troglitazone in type 2 diabetic patients with end-stage renal disease (ESRD). Twelve subjects were randomized to parallel study groups and treated for 6 mo with or without troglitazone at a maximum dose of 600 mg/d in addition to continuing their previous diabetes medications (insulin or sulfonylurea). The results showed no significant differences in glycemic control with or without troglitazone treatment for 6 mo. However, there was a significant reduction in insulin dosage with troglitazone treatment (22.9±7.3 units/d) than without troglitazone treatment (54±12.9 units/d) (p<0.05), as well as the change in the insulin dosage from baseline between the two groups (troglitazone, −8.4 units vs control, +4.3 units, p<0.05). Weight changes and aspartate aminotransferase levels greater than 1.5 times the upper limit of normal were not observed in participants of either treatment group. This study demonstrates that troglitazone was safe and effective for the treatment of hyperglycemia in patients requiring dialysis, and strongly supports the clinical use of currently available TZDs in diabetic patients with renal failure.