New methods are required for sustainable and economical management of bridges. Efficient management can be achieved by a detailed understanding of bridge behavior through monitoring and model-based data interpretation. This paper presents a methodology to evaluate the fatigue safety of existing bridges based on conducting measurements onsite and interpreting measurement data using physics-based behavior models. The methodology combines data from different nondestructive measurements with structural models to develop a suitable set of feasible models that describe accurately structural behavior. The methodology is illustrated with a case study of a composite steel–concrete road viaduct instrumented with acoustic emission channels and strain gauges. Information from measurements is used to update a set of structural models and then evaluate the fatigue safety of the viaduct. While commonly used curve-fitting methods are inaccurate, this methodology is useful to accurately employ the measured behavior of existing civil infrastructure for evaluating nonaccessible elements and scheduling inspections and decision-making related to actions such as strengthening and retrofit.