Accounting for substitution of foods is inevitable when evaluating health impact of dietary changes. But substitution behavior and the associated health impact may vary between individuals. We therefore propose the use of probabilistic methods to model substitution and assess health impact distributions in risk-benefit assessment (RBA) of foods. We investigated the health impact of substituting red and processed meat with fish in the Danish adult population and the variability in health impact. We applied probabilistic approaches in modeling the substitution to reflect variability between individual substitution behaviors. Furthermore, when multiple intake scenarios are compared, we propose a method for adjusting intake differences for individual day-to-day variability. We estimated that 134 (95% UI: 102; 169) Disability-Adjusted Life Years/100,000 were averted per year by the substitution. The health impact varied considerably by age and sex, with the largest health benefit of the substitution observed for young women in the child-bearing age and for the older generation, mainly men. This study provides further insight in how the health impact of substituting meat by fish varies between individuals and suggests a framework to be applied in RBAs of other food substitutions. Our results are relevant for policy makers in defining targeted public health strategies.