Many dietary guidelines recommend restricting the consumption of processed red meat (PRM) in favour of healthier foods such as fish, to reduce the risk of chronic conditions such as hypertension and diabetes. The objective of this study was to estimate the potential effect of replacing PRM for fatty fish, lean fish, red meat, eggs, pulses, or vegetables, on the risk of incident hypertension and diabetes. This was a prospective study of women in the E3N cohort study. Cases of diabetes and hypertension were based on self-report, specific questionnaires, and drug reimbursements. In the main analysis, information on regular dietary intake was assessed with a food frequency questionnaire, and food substitutions were modelled using cox proportional hazard models 95 % confidence intervals were generated via bootstrapping. 71,081 women free of diabetes and 45,771 women free of hypertension were followed for an average of 18.7 and 18.3 years respectively. 2,681 incident cases of diabetes and 12,327 incident cases of hypertension were identified. Replacing PRM with fatty fish was associated with a 15 % lower risk of diabetes (HR = 0.85, 95 CI [0.73: 0.97]), and hypertension (HR =0 .85 [0.79: 0.91]). Between 3 – 10 % lower risk of hypertension or diabetes was also observed when replacing PRM with vegetables, unprocessed red meat, or pulses. The replacement of PRM with alternative protein sources such as fatty fish, unprocessed red meat, vegetables, or pulses was associated with a reduced risk of hypertension and diabetes.