Background:　Depression　and　anxiety　are　among　the　most　prevalent　mental　health　issues　experienced　worldwide.　However,　whereas　cross-cultural　studies　utilize　psychometrically　valid　and　reliable　scales,　fewer　can　meaningfully　compare　these　conditions　across　different　groups.　To　address　this　gap,　the　current　study　aimed　to　psychometrically　assess　the　Brief　Symptomatology　Index　(BSI)　in　42　countries.　Methods:　Using　data　from　the　International　Sex　Survey　(N　=　82,243;　Mage　=　32.39;　SDage　=　12.52;　women:　n　=　46,874;　57　%),　we　examined　the　reliability　of　depression　and　anxiety　symptom　scores　of　the　BSI　-18,　as　well　as　evaluated　evidence　of　construct,　invariance,　and　criterion　-related　validity　in　predicting　clinically　relevant　variables　across　countries,　languages,　genders,　and　sexual　orientations.　Results:　Results　corroborated　an　invariant,　two　-factor　structure　across　all　groups　tested,　exhibiting　excellent　reliability　estimates　for　both　subscales.　The　＇caseness＇　criterion　effectively　discriminated　among　those　at　low　and　high　risk　of　depression　and　anxiety,　yielding　differential　effects　on　the　clinical　criteria　examined.　Limitations:　The　predictive　validation　was　not　made　against　a　clinical　diagnosis,　and　the　full　BSI　-18　scale　was　not　examined　(excluding　the　somatization　sub　-dimension),　limiting　the　validation　scope　of　the　BSI　-18.　Finally,　the　study　was　conducted　online,　mainly　by　advertisements　through　social　media,　ultimately　skewing　our　sample　towards　women,　younger,　and　highly　educated　populations.　Conclusions:　The　results　support　that　the　BSI-12　is　a　valid　and　reliable　assessment　tool　for　assessing　depression　and　anxiety　symptoms　across　countries,　languages,　genders,　and　sexual　orientations.　Further,　its　caseness　criterion　can　discriminate　well　between　participants　at　high　and　low　risk　of　depression　and　anxiety.