BACKGROUND: It remains unclear whether the cardiovascular benefits of physical activity (PA) vary across populations with different predicted atherosclerotic cardiovascular disease (ASCVD) risks. This study aimed to determine the modification of predicted cardiovascular risk on the association between PA and ASCVD incidence. METHODS: A total of 94,734 participants without ASCVD in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project were included, with a median follow-up of 6.0 years. PA volume (metabolic equivalent of task (MET)-h/day) and intensity (%, percentage of moderate-to-vigorous PA (MVPA)) were assessed by questionnaires. Based on the ASCVD 10-year and lifetime risk prediction scores, participants were classified into low-to-medium-risk and high-risk groups. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for ASCVD were calculated using Cox proportional hazards models. RESULTS: During 679,438 person-years of follow-up, 3470 ASCVD events occurred. Higher PA volume was associated with lower ASCVD incidence, which was more pronounced among high-predicted-risk individuals than their low-to-medium-risk counterparts, with HRs (95%CIs) of 0.58 (0.50-0.67) and 0.62 (0.53-0.71) for the highest vs. lowest quartiles of PA volume, respectively. Additionally, analyses for PA intensity showed similar results. Compared with inactive individuals, there was a 32% (95%CI: 25%-38%) and 23% (95%CI: 13%-32%) risk reduction in high- and low-to-medium-risk groups, respectively, when over half of the PA volume was from MVPA. Furthermore, the additive interactions between PA and predicted risk indicated a further risk reduction by increasing PA, especially MVPA, in high-risk individuals. CONCLUSION: Engaging in more PA, especially MVPA, reduced the risk of ASCVD incidence, with greater benefits among high-risk individuals. These findings emphasize the imperative for personalized PA recommendations tailored to distinct risk populations-in particular, reinforcing PA guidance for high-risk individuals.