The relationship between glycemic control and health-related quality of life was examined in patients with non-insulin-dependent diabetes mellitus (NIDDM). Within the context of a randomized controlled trial, 275 patients with NIDDM receiving primary care from a Veteran's Administration general medical clinic were enrolled and monitored for 1 year. Glycemic control (glycosylated hemoglobin levels) and health-related quality of life (Medical Outcomes Study Short-Form 36-item Health Survey [SF-36]) were assessed at baseline and at 1 year. Multivariate regression modeling using baseline and change scores during a 1-year period did not find a linear or curvilinear relationship between glycosylated hemoglobin and SF-36 scores (P = .15); this was true even after controlling for five covariates identified a priori (insulin use, number of diabetic complications, duration of diabetes, education, number of hyper-, or hypoglycemic episodes during the preceding month). Health services researchers and clinicians alike need to be aware that these two important outcomes may not be directly related. This lack of association could contribute to the high noncompliance rates observed among patients prescribed complex diabetic regimens. Unless patients perceive a benefit from following such regimens, good glycemic control may continue to be an elusive therapeutic goal, especially in patients with long-standing disease.