Several studies have tried to analyse the association between all-cause mortality and different risk factors, (especially those which are modifiable, such as smoking, diet or exercise), to develop public health preventive strategies. However, a specific analysis of predictors of premature and late mortality is needed to give more precise recommendations. Considering that there are risk factors which exert an influence on some diseases and not on others, we expect that, similarly, they may have a different impact depending on the timing of mortality, separating premature (<65 years) from late mortality (>65 years). Thus, we prospectively followed-up during a median of 12 years a cohort of 20,272 university graduates comprising an ample range of ages at inception. Time-dependent, covariate-adjusted Cox models were used to estimate adjusted hazard ratios (HR) and their 95 % confidence intervals (CI) for each predictor. The strongest independent predictor of mortality at any age was physical activity which was associated with reduced risk of total, premature and late mortality (range of HRs when comparing the highest vs. the lowest level: 0.24 to 0.48). Specific strong predictors for premature mortality were smoking, HR: 4.22 (95 % CI: 2.42-7.38), and the concurrence of >2 metabolic conditions at baseline, HR: 1.97 (1.10-3.51). The habit of sleeping a long nap (>30 min/d), with HR: 2.53 (1.30-4.91), and poor adherence to the Mediterranean Diet (<3 points in a 0 to 8 score vs. >6 points), with HR: 2.27 (1.08-4.76), were the strongest specific predictors for late mortality. Smoking, diet quality or lifestyles, probably should be differen-tially assessed as specific predictors for early and late mortality. In the era of precision medicine, this approach will allow tailored recommendations appropriate to each person's age and baseline condition.