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Civil infrastructure systems are prone to environmental deterioration processes that gradually reduce their mechanical properties and their capability to sustain severe natural hazards, such as earthquakes. The rate of occurrence of major seismic events, the time-variant seismic vulnerability of single bridges, and the indirect economic losses due to traffic flow redistribution related to the closure of key routes within the highway network are affected by uncertainties to be addressed by modelling their constitutive parameters as random variables and processes. This paper presents an integrated simulation-based methodology to estimate the user cost-based risk and system robustness of spatially distributed bridge networks subjected to prescribed deterioration and regional seismic hazard scenarios. Life-cycle seismic risk metrics are evaluated in terms of bridges failure rates and exceedance rates of indirect monetary losses based on free-flow traffic analysis and user cost assessment. The lifetime system robustness is also evaluated based on appropriate probabilistic performance indicators.