Background:　Research　has　shown　that　some　individuals　can　develop　problematic　patterns　of　online　gaming,　leading　to　significant　psychological　and　interpersonal　problems.　Psychiatric　distress　and　impulsivity　have　been　suggested　to　contribute　to　problematic　online　gaming　(POG).　Objective:　This　study　aimed　to　investigate　the　potential　mediating　or　moderating　mechanisms　of　impulsivity　and　gender-related　differences　in　possible　associations　between　psychiatric　distress　and　POG.　Methods:　A　total　of　596　matched　female　and　male　participants,　ranging　in　age　from　14　to　38　years　(mean　21.4,　SD　4.5),　were　chosen　from　a　large　cross-sectional,　nationwide　Hungarian　online　gaming　sample.　Participants　completed　online　questionnaires　about　self-reported　impulsivity,　psychiatric　distress,　and　POG.　Results:　Psychiatric　distress　directly　predicted　POG,　and　impulsivity　partially　mediated　the　relationship　between　psychiatric　distress　and　POG.　However,　this　mediation　effect　was　found　only　for　the　impatience　factor　of　impulsivity.　Impulsivity　did　not　moderate　the　relationship　between　psychiatric　distress　and　POG.　A　moderating　effect　of　gender　was　not　found　in　the　direct　relationship　between　psychiatric　distress　and　POG.　However,　a　moderated　mediation　analysis　revealed　that　impatience　mediated　the　association　between　psychiatric　distress　and　POG　in　males,　whereas　the　indirect　effect　of　impatience　was　not　significant　in　females.　Conclusions:　The　results　of　this　work　highlight　gender-related　difference　among　online　gamers　in　the　mediation　effect　of　impulsivity　between　psychiatric　distress　and　POG　and　provide　novel　insights　regarding　clinical　implications　for　preventing　or　treating　POG.　©　2019　Journal　of　Medical　Internet　Research.　All　rights　reserved.