Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA(1C) and HOMA-IR (p < 0.05 for all) and increased FMD (p = 0.002). Metformin induced a significant decrease in HbA(1C) (p = 0.02) and only a trend for increase in FMD (p = 0.08). The greater improvement in FMD with pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist.