CONTEXT: Although universal screening for diabetes mellitus is generally not recommended, recent reports suggest that screening individuals with multiple diabetes risk factors may be worthwhile. Little is known about the cost, yield, or acceptability of this kind of screening. PRACTICE PATTERN EXAMINED: Screening of high-risk patients for diabetes mellitus using a two-step, glucose-based screening protocol: Patients were initially screened with a random glucose test; those with abnormal results received a follow-up fasting, 2-hour, 75-gram oral glucose tolerance test. CLINIC SELECTION: Three volunteer clinics from a large medical group in Minnesota. PATIENT SELECTION: Of 38,989 adults receiving care at the three clinics, we identified 1548 high-risk patients with evidence of both dyslipidemia and hypertension in laboratory and administrative databases. Many of these 1548 patients were not eligible for screening: Twenty-five percent already had diagnosed diabetes; 41% had been screened for diabetes in the past year; and 3% had died, disenrolled, or changed clinics before screening commenced. The remaining 30% (n = 469) were invited for diabetes screening. RESULTS: Of the 469 high-risk patients invited, 206 (44%) initiated screening; 176 (38%) completed diabetes screening. Five new patients with diabetes were identified in this high-risk group (one from the random glucose test and four from the glucose tolerance test). One new patient with diabetes was identified for every 40 high-risk patients screened. The program cost $4064 per new case of diabetes identified (screening costs alone). CONCLUSION: In this high-risk managed care population, the yield and acceptability of systematic diabetes screening were low, and the costs were relatively high. The acceptability of office-based diabetes screening may be improved by using a one-step screening test, such as glycosylated hemoglobin, during routine visits.