Examining the performance of an existing bridge requires information on several aspects, such as design choices, material properties, and ongoing degradation processes. It often happens that some critical information is not available. The traditional approach in structural engineering is to take the most conservative assumption for each unknown, following new-design principles. It will often be concluded that structural safety is not ensured and that the bridge must be strengthened or replaced. This conclusion has important economic costs, impacts on users, and environmental burden associated. In this paper, a global data-informed framework is proposed to examine structural safety of existing bridges accurately. Multiple state-of-the-art methodologies are unified to provide a comprehensive framework for bridge examination. Observations, which can include visual inspection, non-destructive testing, and structural sensing, enable the development of more realistic models of structural behaviour. A case study of a reinforced-concrete bridge in Switzerland illustrates the potential of the novel framework. Although almost no information was initially available on the bridge, the monitoring results show that it can be rationally concluded that the bridge is safe. This framework supports engineers in examining existing structures when crucial information is missing based on observations and engineering judgment.