The assessment of existing reinforced concrete (RC) structures, especially, bridges and viaducts, nowadays is one of the most relevant aspects for infrastructural engineers. Due to the old age of a large part of the railways and roadways assets, their safety, especially, with respect to the Ultimate Limit States (ULS) may result compromised. Safety assessment can be performed following different approaches as well as the most sophisticated methodologies based on the application of safety formats for non‐linear finite element (FE) analyses. This study presents the safety assessment at the ULS of existing prestressed RC bridge decks regarding bending moment and axial force failure mechanism adopting different methodologies. Specifically, the safety assessment will be performed through five different approaches (i.e., Courbon theory, elastic FE analysis, and NLFEAs according to the three global safety formats). The decks are modeled using, first, Courbon theory and then, girder FE model composed only of beam elements. The safety assessment is performed by comparing the design resisting moment and design acting moment in the section of interest, therefore, through a local approach. Within the local approach, design values are calculated using the partial safety factors. Afterwards, the decks are modeled with a 3D non‐linear FE model. Three different global safety formats are implemented within a global approach. The application of the different approaches leads to significantly different conclusions about the safety assessment. The two local approaches are the most conservative, therefore, lead to a lower safety margin. The application of global approaches based on global safety formats leads to a safety margin gain compared to local approaches, with significant variability in terms of safety margin gain depending on the specific global safety format.