Seismic　prevention　and　mitigation　of　historical　centers　have　gained　a　central　position　within　earthquake　engineering　topics,　particularly　in　areas　such　as　Italy,　Greece,　and　Portugal.　Many　historical　towns　in　these　countries　have　been　strongly　damaged,　due　to　the　high　quantity　of　old　buildings　and　urban　structures　and　infrastructures.　In　this　article,　these　aspects　are　described,　modeled,　and　investigated　in　terms　of　structural　safety,　the　goal　being　the　set-up　of　a　comprehensive　strategy　for　seismic　prevention　and　mitigation　of　a　whole　historical　center.　The　proposed　approach　is　based　on　two　relevant　parts:　the　first　is　an　urban　risk　assessment,　the　second　is　a　prioritization　of　retrofitting　interventions　so　as　to　optimally　increase　urban　safety.　The　effectiveness　of　the　proposed　methodology　is　shown　with　reference　to　a　complex　case　study,　the　historical　center　of　“Montebello　di　Bertona”.　It　is　initially　modeled　as　a　series/parallel　system　and　then　studied　by　applying　seismic　reliability　methods.　Seismic　retrofitting　interventions　are　finally　prioritized.　©　2017　Taylor　&　Francis.