•Multi-Euler Domain method is updated from 1D to 3D on personal computers.•Most damaging cases for three modern types of bridges are identified.•Different CRFP strengthening schemes on slab-on-girder bridge are evaluated.•Safe distance for cable-stayed bridge pylon under vessel explosions is defined. Since the collapse of the WTC towers in September 2001, concern about the protection of buildings and infrastructures against blast loads has increased significantly. Comprehensive experimental and numerical studies of blast loading effects on buildings have been carried out in recent years, whereas for bridge engineers, blast-resistant design is still a new area which requires separate and systematic investigation. The objective of this paper is to simulate the performance of three modern types of reinforced concrete bridges under various blast loads, including a slab-on-girder bridge, a box-girder bridge and a long-span cable-stayed bridge. To solve the computational constraints in performing numerical analysis on a personal computer, a Multi-Euler domain method based on the fully-coupled Lagrange and Euler models is adopted and further developed for long–span bridge application. This study investigates various detonation scenarios in terms of the explosive weight and location, and their interactions with bridge structures. Both the localized damage mechanism and the global structural response of three bridges are examined. By studying the blast-resistance of each bridge under different explosion threats, the most critical scenarios are identified respectively. Studies of bridge protection against potential attacks by using Carbon Fibre Reinforced Polymer (CFRP) strengthening are also discussed. Numerical results in this study provide bridge owners and engineers with thorough and important information on the structural performance of highway bridges under blast loads, helping them in choosing effective protection strategies for possible potential explosion events.