During　the　last　years,　several　mechanics-based　macromodels　have　been　proposed　to　assess　the　cyclic　response　of　infilled　RC　frames.　However,　the　uncertainties　behind　the　assumptions　on　damage　and　failure　mechanisms　compromise　the　reliability　of　such　approaches.　For　this　reason,　this　paper　proposes　a　new　data-driven　hysteresis　model　for　the　cyclic　response　of　infilled　RC　frames.　The　infill　panel　is　schematized　as　a　single-degree-of-freedom　element,　whose　constitutive　law　is　given　by　the　proposed　hysteresis　model.　The　model　combines　a　degrading　Bouc-Wen　element　with　a　slip-lock　element,　which　is　introduced　specifically　to　reproduce　the　pinching　effect　due　to　crack　openings　in　the　masonry　panel.　The　parameters　governing　the　model　have　clear　physical　meanings　and　are　calibrated　on　the　basis　of　an　experimental　data　set　of　cyclic　responses　of　single-story　single-bay　RC　infilled　frames.　The　calibrations　are　carried　out　by　means　of　a　genetic　algorithm-based　optimization.　Analytical　correlation　laws　linking　the　model　parameters　with　geometric　and　mechanical　properties　of　the　RC　infilled　frame　are　proposed　and　validated　by　blind　validation　tests.　Results　show　adequate　accuracy　of　the　model　in　reproducing　the　cyclic　response　of　infilled　frames　characterized　by　significantly　different　geometrical　and　mechanical　features.　The　model　is　defined　by　a　smooth　analytical　hysteresis　law,　with　great　advantages　regarding　numerical　stability　and　computational　effort.　This　makes　it　suitable　for　dynamic　and　stochastic　simulations.　©　2021　American　Society　of　Civil　Engineers.