With new diabetes diet guidelines recommending high carbohydrate intake, questions arise regarding acceptable intake of simple sugars. Whereas several short-term studies report flattened glycemic and insulin response to fructose consumption, some also report increased serum triglyceride levels. Few studies examine the effects of long-term fructose consumption. We evaluated the long-term safety of fructose consumption in 14 middle-aged men with diabetes. Subjects followed an ambulatory high-fiber high-carbohydrate control diet at home for 8 wk, entered the hospital for 5 days on this diet, and spent the next 7 days on a similar diet supplemented with 50–60 g fructose. They continued the fructose diet at home for 23 wk, then resumed a postcontrol diet for an additional 16 wk. In the hospital, glycemic control improved significantly on the fructose-supplemented diet compared with the hospital control diet. In the ambulatory setting, no significant differences in plasma glucose, glycohemoglobin, serum cholesterol, triglycerides, lactate, or urate occurred between precontrol, fructose, or postcontrol periods. Fasting serum lactate was higher by 0.5 meq/L during the ambulatory fructose period than during the precontrol period. Body weight also increased during the ambulatory fructose period due to higher calorie intake. Adherence to fructose consumption was excellent and improved adherence to carbohydrate and fat recommendations. If total calorie intake is controlled to promote desirable body weight, crystalline fructose used with a high-carbohydrate high-fiber low-fat diet appears to be safe and acceptable for diabetic individuals.