Background A lifestyle cardiovascular risk score ( LCRS ) and a genetic risk score ( GRS ) have been independently associated with myocardial infarction ( MI ) in Hispanics/Latinos. Interaction or joint association between these scores has not been examined. Thus, our aim was to assess interactive and joint associations between LCRS and GRS , and each individual lifestyle risk factor, on likelihood of MI . Methods and Results Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 matched controls. The LCRS used estimated coefficients as weights for each factor: unhealthy diet, physical inactivity, smoking, elevated waist:hip ratio, low/high alcohol intake, low socioeconomic status. The GRS included 14 MI ‐associated risk alleles. Conditional logistic regressions were used to calculate adjusted odds ratios. The odds ratios for MI were 2.72 (2.33, 3.17) per LCRS unit and 1.13 (95% CI 1.06, 1.21) per GRS unit. A significant joint association for highest GRS tertile and highest LCRS tertile and odds of MI was detected (odds ratio=5.43 [3.71, 7.94]; P <1.00×10 ⁻⁷ ), compared to both lowest tertiles. The odds ratios were 1.74 (1.22, 2.49) under optimal lifestyle and unfavorable genetic profile, and 5.02 (3.46, 7.29) under unhealthy lifestyle but advantageous genetic profile. Significant joint associations were observed for the highest GRS tertile and the highest of each lifestyle component risk category. The interaction term was nonsignificant ( P =0.33). Conclusions Lifestyle risk factors and genetics are jointly associated with higher odds of MI among Hispanics/Latinos. Individual and combined lifestyle risk factors showed stronger associations. Efforts to improve lifestyle behaviors could help prevent MI regardless of genetic susceptibility.