Introduction The new SCORE2 provides risk estimates for the combined outcome of fatal and non-fatal cardiovascular disease (CVD) events, in contrast with SCORE's use for CVD mortality only. Genetic predisposition to CVD is not considered in SCORE2 for prevention and treatment. Purpose Evaluate the impact of adding a Genetic Risk Score (GRS) to the new European SCORE2 in MACE prediction and estimate the additional value in cardiovascular risk stratification in an asymptomatic Portuguese population. Methods A prospective study was performed in a population-based cohort of 1,100 individuals without known CVD and diabetes (mean age 53.3±6.9 years). For all included participants, SCORE2 was calculated and three risk categories were considered: low-, moderate- and high-risk. A 33-SNP GRS was constructed and two groups were analyzed: lower and higher than the GRS median. Kaplan-Meier survival curves were created and a Cox regression model was performed with the two scores to assess MACE risk. C-statistic methodology compared the model between SCORE2 solely and SCORE2 plus GRS. Results After Kaplan-Meier analysis for MACE occurrence, the high categories of SCORE 2 and GRS showed worst survival when compared to the lower categories (p Conclusions In this work, combining SCORE2 with multiple genetic loci gathered into a GRS, improved the identification of patients with the worst prognosis. This new tool may be of great utility in risk stratification in primary prevention. Larger prospective multicenter cohorts with longer follow-up should reproduce and validate these findings. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM