Progressive　structural　collapse　is　a　typical　low-probability　high-consequence　event.　Progressive　collapse　design　can　effectively　improve　the　robustness　of　structures　against　accidental　local　damage　and　reduce　the　probability　of　collapse.　However,　progressive　collapse　design　also　increases　the　construction　cost　of　buildings.　Hence,　it　is　necessary　to　conduct　cost-benefit　analyses　for　the　progressive　collapse　design　of　building　structures.　This　study　first　designs　a　reinforced　concrete　(RC)　frame　based　on　a　progressive　collapse　design　program　that　simultaneously　optimizes　material　consumption　and　structural　resistance.　Then,　the　structural　failure　probability　is　quantified　using　an　alternative　path　(AP)　method-based　fragility　analysis　that　considers　the　structural　uncertainties.　Based　on　this,　the　life　cycle　costs　and　benefits　of　the　structure　designed　with　different　design　load　factors　are　investigated.　A　four-story　RC　frame　is　used　as　an　example.　By　considering　the　time　value　of　money　and　threat　probability,　the　break-even　points　and　optimized　design　load　factors　for　the　progressive　collapse　design　of　the　RC　frame　are　analyzed.　These　research　outcomes　can　help　promote　progressive　collapse　design　in　engineering　practice　and　provide　references　for　proposing　scientific　and　reasonable　design　load　factors.