BACKGROUND: Our objective was to analyze a restricted carbohydrate dietary approach compared to a standard low-fat diet plus medication plan as treatment for weight loss and the metabolic syndrome. METHODS: This was a retrospective analysis of patients attending an outpatient weight and metabolism management program, including periodic individual visits combined with either a carbohydrate-restricted diet (with multivitamin and essential fatty acids supplementation) or low-fat/low-calorie diet + phentermine/fenfluramine. The main outcome measurements were total body weight and fasting serum lipid profiles. Clinical data were maintained on standardized flow sheets. RESULTS: One hundred twenty-two patients had complete baseline and follow-up information. Sixty-six were treated with a carbohydrate-restricted diet without medication, and 56 were treated with a combination of low-fat/low-calorie diet and medication. Weight loss occurred in both groups, but was greater in the medication group: the carbohydrate-restricted group lost a mean of 9.5 kg over 15.0 weeks (0.63 kg/week); the low-fat/low-calorie diet + medication group lost a mean of 14.1 kg over a mean duration of 20.2 weeks (0.70 kg/week), p < 0.01. The carbohydrate-restricted group had a greater reduction in triglycerides (p = 0.02) and triglyceride/HDL ratio (p = 0.01), and a greater increase in HDL (p < 0.001) than the medication group. CONCLUSIONS: In this outpatient program, a carbohydrate-restricted diet and a low-fat/low-calorie diet + medication led to weight loss, but the carbohydrate-restricted diet had a more favorable effect on triglycerides and HDL. Because of the effects on weight, triglycerides, and HDL, a carbohydrate-restricted diet may be useful for the treatment of metabolic syndrome.