BACKGROUND: A vegetarian diet may lead to numerous health benefits, including weight loss. OBJECTIVE: We examined the joint effects of personal preference of dietary treatment and a calorie-restricted, low-fat lactoovovegetarian diet (LOV-D) compared with a standard calorie-restricted, low-fat omnivorous diet (STD-D) on changes in weight, total cholesterol, ratio of LDL to HDL cholesterol (LDL:HDL cholesterol), triacylglycerols, insulin resistance, and macronutrient intake during an 18-mo study. DESIGN: This was a randomized clinical trial of 176 overweight and obese adults who were recruited and randomly assigned first to 1 of 2 preference conditions (yes or no). If assigned to Preference-No, they were randomly assigned to 1 of the 2 diet conditions (STD-D or LOV-D). If assigned to Preference-Yes, they were assigned to the diet they indicated as preferred at screening. The 12-mo intervention was followed by a 6-mo maintenance phase. RESULTS: Participants were mainly women (86.9%) and white (70.5%); 75% completed the 18-mo study. A significant interaction between preference and dietary treatment was not observed for any of the outcome variables. However, participants in the Preference-No groups significantly decreased their triacylglycerols (P = 0.04). The only effect observed for diet was a borderline significant decrease in LDL:HDL cholesterol for the LOV-D group (P = 0.06). Within the LOV-D groups, those who were 100% adherent to the LOV-D had significant and marginally significant reductions in monounsaturated fat (P = 0.02) and total fat (P = 0.05) intakes at 18 mo. CONCLUSIONS: Our findings suggest that neither prescribing a vegetarian diet nor allowing persons to choose their preferred diet had a significant effect on outcome measures. However, all participants had a significant reduction in total energy and fat intakes and an increase in energy expenditure, which was reflected in reduced body weight. This clinical trial was registered at www.clinicaltrials.gov as NCT00330629.