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Background: Prior research on alcohol consumption and pain has yielded inconsistent results regarding the directionality of effects for both consumption-to-pain and pain-to-consumption relations. The present study sought to examine directionality of these relations by testing bidirectional longitudinal associations between consumption and pain interference, a crucial aspect of pain that captures pain-related disability and has been regarded as a valuable measure of treatment outcome. In addition, this study explored possible moderation of these bidirectional longitudinal associations by gender and alcohol use disorder (AUD) symptomatology., Methods: Analyses included 29,989 current/former drinkers who were interviewed at both waves (2001 and 2004) of the U.S. National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Analyses used self-report data from both waves on past-year average daily volume of alcohol consumed and past-month pain interference (1 item from the Medical Outcomes Study 12-item Short-Form Health Survey [MOS-SF-12]). AUDADIS-IV data from Wave 1 were used to index baseline AUD symptomatology (i.e., symptom count). Cross-lagged panel modeling and multigroup analyses were employed., Results: Regarding the consumption-to-pain-interference relation, in general, higher baseline alcohol consumption was associated with lower subsequent pain interference at follow-up. However, among men with higher AUD-symptom counts, the opposite pattern emerged, with higher baseline alcohol consumption being significantly related to higher subsequent pain interference at follow-up. Regarding the pain-interference-to-consumption relation, higher baseline pain interference was significantly associated with lower subsequent alcohol consumption at follow-up, and no moderating effects were observed., Conclusions: The distinctive patterns of the consumption-to-pain-interference relation observed among men with elevated AUD symptomatology suggest that this relation might be driven by different mechanisms across different groups of individuals. Specifically, the detrimental effect of alcohol on pain interference might emerge at relatively advanced stages of AUD among men, consistent with Koob's Dark Side of Alcohol Addiction theory in human research., (© 2020 by the Research Society on Alcoholism.)