OBJECTIVES: Diabetes Mellitus (DM) patients typically suffer from comorbid conditions and disease-related macro- and microvascular complications which, in conjunction to demographic, anthropometric, clinical and treatment satisfaction variables, have a confounding effect on health-related quality of life. Therefore, discriminative ability of measuring instruments is important. Three preference-based utility instruments were assessed in terms of their sensitivity to a common complication of diabetes, i.e. coronary heart disease (CHD). METHODS: 319 Type II DM patients (62.4% female, mean age 65.3) were surveyed with the 15D, EQ-5D, SF-36 and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Independent variables including gender, age, years with diabetes, BMI, HbA1c, treatment satisfaction, and existence of hypertension, hyperlipidaemia, COPD, arthropathy, vascular disease, diabetic foot, retinopathy, neuropathy and nephropathy were introduced in univariate regression models to identify significant predictors of 15D, EQ-5D and SF-6D utilities. RESULTS: DM patients with CHD (N=107, 61.7% female, mean age 71.0) reported lower utilities than DM patients without: 15D, 0.740 vs. 0.841; EQ-5D, 0.627 vs. 0.756; SF-6D, 0.708 vs. 0.775, (P<0.001 throughout). The regression models explained 51.1%, 39.6% and 28.0% of 15D, EQ-5D and SF-6D variance respectively. Five common significant predictors (gender, age, treatment satisfaction, arthropathy and diabetic foot), and five others significant in at least one model were identified, which were controlled for with ANCOVA. The respective results (CHD, yes vs. no) were: 15D, 0.787 vs. 0.817, P<0.05; EQ-5D, 0.702 vs. 0.718, P=0.589; SF-6D, 0.737 vs. 0.761, P=0.084. CONCLUSIONS: After correcting for the confounding effect of common diabetes variables, only the 15D produced statistically significant HRQoL differences between DM patients with and without CHD, most likely due to its richer descriptive system. This increased sensitivity is perhaps evidence in favour of the 15D in diabetics suffering from CHD, but concurrently emphasizes the need for further testing in larger and more diverse DM patient samples.