Background & aims: While most studies have shown increased mortality associated with excessive red/processed meat consumption, the association of saturated fatty acids (SFA) intake with mortality is less homogeneous. We aimed to prospectively assess the association of both, meat consumption (red, processed, red + processed, and total) and SFA intake, with the risk of all-cause death. Methods: We assessed 18,540 participants of the SUN (Seguimiento Universidad de Navarra) cohort, followed-up for a mean of 9.5 years. A validated 136-item FFQ was administered at baseline. We used Cox models adjusted for potential confounders. Results: We observed 255 deaths during 176,916 person-years of follow-up. Age modified the association between meat consumption and all-cause mortality (p for interaction = 0.027, 0.075, and 0.013, for red, total, and processed meat, respectively). Among participants aged >45 years the fully-adjusted HRs (95% CIs) for one additional serving/d of red, total, and red + processed meat consumption were 1.47 (1.06, 2.04), 1.23 (1.05, 1.45), and 1.32 (1.05, 1.65), respectively, with significant linear trends (P for trend 0.022, 0.012, and 0.018, respectively). In these participants, SFA intake was non-significantly associated with mortality. However, isocaloric replacement of monounsaturated fat or carbohydrates by SFA resulted in significantly higher mortality risk. Likewise, replacing 100 g of vegetables, fruits & nuts or cereals by 100 g of red meat resulted in higher mortality risk. No association of meat consumption or SFA with all-cause mortality was observed in participants younger than 46 years. Conclusions: Among highly educated persons, aged >45 years, a high consumption of red, total, and red + processed meat was related to increased all-cause mortality, compared with those with low consumption, whereas no significant associations were found for SFA intake. Dietary guidelines should specifically limit meat consumption and not relying only in limiting SFA intake. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.