Abstract Body (Do not enter title and authors here): Background: The relationship between body weight changes and survival after stroke diagnosis is complex and influenced by various factors. While higher levels of physical activity (PA) are known to improve post-stroke outcomes, it remains unclear whether PA status can impact the association between body weight changes and survival in stroke patients. This study tested the hypothesis that sustained moderate to vigorous physical activity (MVPA) modifies the association between body weight changes and all-cause and cardiovascular mortality in stroke survivors. Methods: This retrospective study followed 32,905 ischemic stroke patients registered with the National Health Insurance Service. Body mass index (BMI) and PA were measured for three years prior to and two years following stroke diagnosis. Changes in BMI were classified as BMI loss, BMI stable, and BMI gain, while changes in MVPA were classified as persistently inactive, MVPA initiation, MVPA quitting, or MVPA continuation. Outcomes included all-cause mortality (ACM) and cardiovascular mortality (CVM). Results: During a median follow-up of 6 years, we identified 4,379 cases of ACM and 1,349 cases of CVM. In adjusted models compared with the stable BMI-inactive, the hazard ratios (HRs) indicated a higher risk of ACM (HR 1.68, 95% CI 1.42-1.98) and CVM (HR 1.74, 95% CI 1.30-2.33) in the BMI loss-inactive, and a higher risk of ACM (HR 1.66, 95% CI 1.40-1.96) and CVM (HR 1.89, 95% CI 1.40-2.54) in the BMI loss-MVPA quitting. However, these risks were not observed in the BMI loss-MVPA continuation (HR 1.00, 95% CI 0.85-1.18 for ACM; HR 0.96, 95% CI 0.72-1.29 for CVM). Conversely, the BMI gain-MVPA continuation had a lower risk of ACM (HR 0.72, 95% CI 0.61-0.85) and CVM (HR 0.74, 95% CI 0.54-1.00), but this was not observed in the BMI gain-inactive (HR 0.95, 95% CI 0.79-1.15 for ACM; HR 0.89, 95% CI 0.64-1.24 for CVM), compared with the stable BMI-inactive. Conclusions: Sustained MVPA significantly modifies the association between body weight changes and survival in ischemic stroke survivors. Body weight loss combined with inactive increases the risk of death, whereas continued MVPA mitigates these risks. Body weight gain with ongoing MVPA is associated with lower mortality risks. These findings highlight the importance of sustained PA in improving survival outcomes post-stroke and suggest that PA plays a crucial role in modulating the obesity paradox in stroke patients.