Abstract Objective To estimate effects of weight change on incidence of major cardiovascular events in the Italian population-based Progetto CUORE. Methods Prospective observation in 12 Italian population-based cohorts on etiology of cardiovascular disease. Twenty-thousand six-hundred-forty-seven men and women aged 35–69 years without previous CVD, examined at baseline between 1984 and 1993 and followed for median time 8.5 years, with validated first cardiovascular events. Standardised anthropometric variables, lifestyle and biochemical risk factors for CVD; major cardiovascular events as end-points. Results Linear regression between BMI and major CVD risk factors was combined with Cox coefficients from a prediction model of CVD, CHD and stroke using major risk factors as dependent variables. Estimated cardiovascular risk reductions with BMI lowered by 1 to 3 U were: for men 3.8% to 10.9% for all cardiovascular events, 4.2% to 12.1% for CHD, and 2.3% to 6.9% for stroke; for women 2.8% to 8.1% for all cardiovascular events, 3.4% to 9.8% for CHD, and 2.1% to 6.2% for stroke. Conclusions Body weight level influences cardiovascular disease risk in the Italian population.