Aim: To compare the efficacy, safety and tolerability of adding rosiglitazone (RSG) vs. sulphonylurea (SU) dose escalation in older type 2 diabetes mellitus (T2DM) patients inadequately controlled on SU therapy. Methods: A total of 227 T2DM patients from 48 centres in the USA and Canada, aged ≥60 years, were randomized to receive RSG (4 mg) or placebo once daily in combination with glipizide 10 mg twice daily for 2 years in a double-blind, parallel-group study. Previous SU monotherapy was 1/4 to 1/2 maximum recommended dose for ≥2 months prior to screening with fasting plasma glucose (FPG) ≥7.0 and ≤13.9 mmol/l. Treatment options were individualized, and escalation of study medication was specifically defined. Results: Disease progression (time to reach confirmed FPG ≥10 mmol/l while on maximum doses of both glipizide and study medication or placebo) was reported in 28.7% of patients uptitrating SU plus placebo compared with only 2.0% taking RSG and SU combination (p <0.0001). RSG + SU significantly decreased HbA1c, FPG insulin resistance, plasma free fatty acids and medical care utilization and improved treatment satisfaction compared with uptitrated SU. Conclusions: Addition of RSG to SU in older T2DM patients significantly improved glycaemic control and reduced disease progression compared with uptitrated SU alone but without increasing hypoglycaemia. These benefits were associated with increased patient treatment satisfaction and reduced medical care utilization with regards to emergency room visits and length of hospitalization. Early addition of RSG is an effective treatment option for older T2DM patients inadequately controlled on submaximal SU monotherapy. © 2005 Blackwell Publishing Ltd.