Processed meat and red meat have been associated with increased mortality, but studies are inconsistent and few have investigated substitution by other protein sources. The relationship of overall and causes-specific mortality with red meat, processed meat, and other dietary protein sources was investigated in The Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69years provided information on dietary and lifestyle habits. Mortality follow-up until 1996 consisted of linkage to statistics Netherlands. Multivariable case-cohort analyses were based on 8823 deaths and 3202 subcohort members with complete data on diet and confounders. Red meat (unprocessed) intake was not associated with overall and cause-specific mortality. Processed meat intake was significantly positively related to overall mortality: HR (95% CI) comparing highest versus lowest quintile, 1.21 (1.02-1.44) with P-trend=0.049. Significant associations were observed for cardiovascular [HR Q5 vs. Q1, 1.26 (1.01-1.26)] and respiratory [HR=1.79 (1.19-2.67)], but not cancer mortality [HR=1.16 (0.97-1.39)]. Adjustment for nitrite intake attenuated these associations which became nonsignificant: HRs Q5 versus Q1 (95% CI) were: 1.10 (0.77-1.55) for total, 1.09 (0.71-1.67) for cardiovascular, 1.44 (0.68-3.05) for respiratory, and 1.11 (0.78-1.58) for cancer mortality. Nitrite was significantly associated with overall, CVD and respiratory mortality. Poultry intake was significantly inversely related to cancer and overall mortality. While fish intake showed positive associations, nut intake showed inverse associations with all endpoints. Replacing processed meat with a combination of poultry, eggs, fish, pulses, nuts and low-fat dairy was associated with lower risks of overall, cardiovascular and respiratory mortality. Processed meat was related to increased overall, CVD and respiratory mortality, potentially due to nitrite. Substituting processed meat with other protein sources was associated with lower mortality risks.