It is likely that the Mediterranean diet (MedDiet) may mitigate the adverse effects of obesity on the incidence of type 2 diabetes mellitus (T2DM). We assessed this hypothesis in a cohort of 18 225 participants initially free of diabetes (mean age: 38 years, 61 % women). A validated semi-quantitative 136-item FFQ was used to assess dietary intake and to build a 0-9 score of adherence to MedDiet. After a median of 9.5-year follow-up, 136 incident cases of T2DM were confirmed during 173 591 person-years follow-up. When MedDiet adherence was low (4 points), the multivariable-adjusted hazard ratios (HR) were 4.07 (95 % CI 1.58, 10.50) for participants with BMI 25-29.99 kg/m(2) and 17.70 (95 % CI 6.29, 49.78) kg/m(2) for participants with BMI >= 30 kg/m(2), (v.<25 kg/m(2)). In the group with better adherence to the MedDiet (>4 points), these multivariable-adjusted HR were 3.13 (95 % CI 1.63, 6.01) and 10.70 (95 % CI 4.98, 22.99) for BMI 25-30 and >= 30 kg/m(2), respectively. The P value for the interaction was statistically significant (P=0.002). When we assessed both variables (BMI and MedDiet) as continuous, the P value for their interaction product-term was marginally significant (P=0.051) in fully adjusted models. This effect modification was not explained by weight changes during follow-up. Our results suggest that the MedDiet may attenuate the adverse effects of obesity on the risk of T2DM.