Abstract only Introduction: Sex differences in the systolic blood pressure (SBP) trajectories have been described previously. However, the contribution of underlying genetic architecture to the sex associated differences in SBP trajectories has not been assessed. Methods: Multiancestry sex-specific SBP polygenic risk scores (SBP-PRS), accumulating 1.1 million variants each, were calculated in the participants of the ARIC, JHS, CARDIA, CHS, MESA, FHS, and JHS who underwent whole genome sequencing under the TransOmics for Precision Medicine Program. Based on the SBP-PRS, the cohort was stratified into low (<20 th centile), intermediate (20 th -80 th centile), and high (>80 th centile) genetic risk of SBP. For individuals on antihypertensive medications, SBP measurements were corrected by adding 15 mmHg. Multivariable adjusted restricted cubic splines were used to depict the non-linear relationship of SBP with age in each sex separately. Bootstrapping using 1000 samples was used to estimate the age and 95% CIs at which the sex-specific SBP trajectories crossed over in each SBP-PRS group. Results: In this study of 21,542 individuals (median age: 56 years; 56.0% females; 35.8% non-White individuals), the non-linear association of SBP with age varied by sex (P interaction : <0.001) and SBP-PRS groups (P interaction : 0.05). On stratifying by SBP-PRS, females had a higher age-related increase in SBP compared with males across the groups (p<0.001 in low, intermediate, and high SBP-PRS groups). The age at which the SBP in females surpassed that of males progressively decreased with increasing genetic risk of SBP low: 66.7 (66.4-67.0) years, intermediate: 64.3 (64.1-64.6) years, high: 55.8 (54.4-57.1) years; p: <0.001. In the high SBP-PRS group, the sex-associated differences in SBP trajectories were modest with females and males having nearly similar SBP values in old age. Conclusion: The underlying genetic architecture may contribute to sex difference of SBP trajectories.