Real behavior of existing structures is usually associated with large uncertainty that is often covered by the use of conservative models and code practices for the evaluation of remaining fatigue lives. In order to make better decisions related to retrofit and replacement of existing bridges, new techniques that are able to quantify fatigue reserve capacity are required. This paper presents a population-based prognosis methodology that takes advantage of in-service behavior measurements using model-based data interpretation. This approach is combined with advanced traffic and fatigue models to refine remaining-fatigue-life predictions. The study of a full-scale bridge demonstrates that this methodology provides less conservative estimations of remaining fatigue lives. In addition, this approach propagates uncertainties associated with finite-element, traffic and fatigue-damage models to quantify their effects on fatigue-damage assessments and shows that traffic models and structural model parameters are the most influential sources of uncertainty.