Objective: We sought to examine patients' preferences regarding the design of diabetes trials. Specifically, do patients prefer trials to focus on patient-important outcomes (vs. surrogate outcomes) and provide practical/pragmatic answers (vs. mechanistic/explanatory answers)? Study Design and Setting: We mailed a questionnaire to a stratified random sample of 4,796 patients with diabetes receiving care from 371 primary care clinicians in the US Midwest. Medical record review provided data on hemoglobin A1c (HbA1c). Descriptive statistics, logistic regression, and multiple regression techniques were used for analysis. Results: We received completed surveys from 2,036 patients (response rate of 42.5%). On average, respondents were 65 years old, had 11 years of diabetes, and had excellent glycemic control (HbA1c = 7%). Most patients (>75%) chose patient-important outcomes rather than HbA1c as their first choice for a trial primary outcome and preferred a practical trial design. Patients with poor glycemic control (HbA1c > 8.0%) were more likely to prefer HbA1c as a primary end point (odds ratio: 1.5; 95% confidence interval: 1.1, 2.1). Conclusion: Individuals with diabetes report a strong preference for practical trials measuring the effect of treatments on patient-important outcomes. To our knowledge, this is the first report of patients endorsing key elements of the comparative effectiveness agenda. © 2011 Elsevier Inc. All rights reserved.