OBJECTIVES: overweight and other cardiovascular risk factors are known contributors to disability accrual in Multiple Sclerosis (MS). We aimed to explore the impact of three hypocaloric dietetic patterns, based on the Mediterranean diet, on cardiovascular risk and clinical status in overweight persons with MS (pwMS). MATERIAL AND METHODS: overweight pwMS (body mass index-BMI ≥25 kg/m RESULTS: fifty-three patients completed the study (diet A n = 19, diet B n = 18, diet C n = 16). The three groups were well matched for sex, age, disease duration and EDSS. Along the 6 months of dietetic intervention, no difference in adherence was detected across the three dietetic plans (p = 0.84). Overall, patients showed a significant weight loss over time (p <
0.001) with no difference across diets (p = 0.34). BMI, WC, UC, HC and cholesterol improved over time (p ranging from 0.06 to 0.001), with no differences across diets (p ranging from 0.16 to 0.58). Among all tested clinical variables, fatigue, anxiety, information processing speed and manual dexterity improved significantly (p = 0.005, p = 0.012, p = 0.013, p = 0.005), with no differences across diets (p = 0.84, p = 0.89, p = 0.53, p = 0.72). CONCLUSION: dietetic interventions in overweight pwMS, irrespective of their specific macronutrients composition, are able to improve the cardiovascular profile, the perception of subjective symptoms as well as objective disability scores.