Stroke is the second leading cause of death and contributes to significant disability among individuals who have experienced it. With recent identification of various risk variants for stroke and the development of genetic risk scores that predict stroke incidence, the estimation of lifetime risk of stroke (LTRS) has become possible. A cohort study in the United States followed 11,568 adults aged 45 to 64 who were all free of stroke or transient ischemic attack at baseline for a median of 28 years. The LTRS was estimated according to levels of genetic risk based on a polygenic risk score (PRS) and also to levels of cardiovascular health based on the American Heart Association Life’s Simple 7 (LS7) recommendations (stopping smoking, eating better, getting activity, losing weight, managing blood pressure, controlling cholesterol, and reducing blood sugar). For the findings, it is no wonder that people with high genetic risk and inadequate cardiovascular health had the shortest overall survival and survival free of stroke, while those with low genetic risk and an optimal cardiovascular health had the longest. Yet, even with a preceding high PRS, the LTRS can be mitigated by up to 43% if adhering to the LS7 for healthy lifestyle, which can be translated into 6 more years living free of stroke.