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Background: Previous work on gene‐environment (GxE) interplay concerning anxiety has focused on the interaction of 5‐HTTLPR with childhood adversities or traumatic events whereas the impact of recent stressors is understudied, as is the integration of resilience. The current study aimed to investigate the interactive effect of 5‐HTTLPR and recent stress on anxiety in adolescents considering resilience as buffer of a GxE risk constellation. Method: In a random population‐based sample of 14–21 years old from Dresden, Germany, (N = 1180; genotyped = 942) recent stress (Daily Hassles [DH] Scale, Perceived Stress Scale, Screening Scale of the Trier Inventory for the Assessment of Chronic Stress), resilience (Connor–Davidson resilience scale) and anxiety (Patient Reported Outcome Measurement Information System Anxiety Short Form) were assessed via questionnaire in 2015 or 2016. Results: Fractional regression models revealed that resilience interacted with recent stress in form of DH as well as recent chronic stress and 5‐HTTLPR regarding anxiety. Participants carrying the more active LALA genotype reported consistently higher levels of anxiety when experiencing more DH or more recent chronic stress and having low levels of resilience. When the resilience scores were high, LALA carriers reported the lowest anxiety scores despite DH or recent chronic stress. Conclusion: Findings revealed an interactive relationship between 5‐HTTLPR genotype and recent stress suggesting resilience to function as an additional dimension buffering the impact of a GxE risk constellation. Early interventions to build resilience may be useful to prevent an escalation of distress and associated unfavorable health outcomes. [ABSTRACT FROM AUTHOR]