The　spread　of　antibiotic　resistance　genes　(ARGs),　including　intracellular　ARGs　(i-ARGs)　and　extracellular　ARGs　(e-ARGs),　has　become　a　global　problem　that　cannot　be　ignored.　This　study　clarified　the　fates　of　e-ARGs　and　i-ARGs　in　floc　sludge　reactor　(FS),　granular　sludge　reactor　(GS)　and　biofilm　reactor　(BF)　under　the　stress　of　acetaminophen　(APAP).　The　results　showed　that　the　risk　of　ARGs　transmission,　especially　for　e-ARGs,　in　FS　and　BF　could　increase　with　the　increasing　times　of　APAP　treatment,　except　for　that　in　GS.　The　fates　of　i-ARGs　in　three　different　systems　were　similar,　which　were　mainly　clustered　as　the　efflux　pumps　mechanism.　The　secretion　and　disintegration　of　extracellular　polymeric　substances　mainly　affected　the　fates　of　e-ARGs.　In　the　three　systems,　the　complexity　of　network　relationships　between　ARGs　and　microbial　communities　was　FS,　GS　and　BF.　Partial　least-squares　path　model　analysis　indicated　that　bacterial　community　directly　contributed　to　the　variations　of　e-ARGs　and　i-ARGs　under　APAP　treatment　in　the　three　systems,　playing　a　leading　role.　And　i-ARGs　and　protein　secondary　structure　showed　direct　effects　on　e-ARGs.　This　study　indicated　that　e-ARGs　in　complex　systems　were　more　susceptible　to　be　influenced,　which　should　be　paid　more　attention　to　prevent　further　propagation　of　ARGs.　©　2023　Elsevier　B.V.