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Background: Using meal replacement plans is one of the weight loss methods. A study on the effectiveness and efficiency of these methods seems necessary. In this study, we intend to determine and compare the effectiveness of Meal Replacement Therapy (MRT) and the Usual Low-Calorie diet (ULC) on Resting Metabolic Rate (RMR) and body composition in overweight and obese women. Methods: This quasi-experimental clinical trial consisted of two groups of women aged 18 to 50 years with a BMI of 25 to 40. Participants were allowed to choose between MRT and ULC diets based on their preferences. Both groups received equal daily calories (1000-1200 kcal in the first four weeks and 1200-1400 kcal in the second four weeks), which BMI determined. Primary outcomes were BMI, weight, body composition, and RMR. Secondary outcomes were Fasting Plasma Glucose (FPG), insulin, lipid profile, and Physical symptoms. Results: There were 35 participants in each group. There were no significant differences in the baseline anthropometric and metabolic measurements between the two groups (p>0.05). The only significant difference between the two groups was weight and BMI, lower in the MRT group (28.48kg/m2 vs. 30.75kg/m2). RMR did not change in the MRT group but decreased significantly in the ULC group. Metabolic profile improved in both groups, but no significant difference was observed between the two groups (p>0.05). Conclusion: The results of this study showed that meal replacement therapy is a more effective strategy for losing weight.Nevertheless, it is necessary to do further studies on meal replacements. Trial registration The study was approved on January 19, 2020, in the Mashhad University of Medical Sciences (ethics code: IR.MUMS.MEDICAL.REC.1398.744) as well as in the Iranian Registry of Clinical Trials (IRCT code: IRCT20200611047731N1. Registration date: 17-07-2020)