Background and Aim. To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years. Materials and Methods. A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40–59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer (n = 459) and cardiovascular deaths (n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models. Results. A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine–Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma. Conclusions. A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction.