BACKGROUND: Research on caffeine and cognitive performance remains controversial. Variations in genes associated with caffeine metabolism and response such as AIM: To investigate caffeine × gene interactions on cognitive performance in all key domains of cognition in healthy individuals. METHODS: Participants completed a lifestyle and food frequency questionnaire and a cognitive test battery including validated tasks to assess the domains of social cognition, memory, attention and executive function. Genotyping was performed for RESULTS: Significant gene × caffeine interactions were observed for the domains of social cognition, ( CONCLUSIONS: The present findings suggest an association between genetic caffeine metabolism, habitual caffeine intake and cognitive function in the domains of social cognition and executive function. More research in naturalistic environments using larger cohorts is needed to confirm these findings to add to our understanding of how habitual caffeine may influence cognitive function based on individual genotype.