This study investigates the health risks associated with prolonged occupational sitting and whether there is a threshold of physical activity that can mitigate these risks. The research, conducted in Taiwan, followed 481,688 participants over a mean period of 12.85 years. The study found that individuals who predominantly sat at work had a 16% higher risk of all-cause mortality and a 34% higher risk of cardiovascular disease (CVD) mortality compared to those who predominantly did not sit at work. However, individuals who alternated between sitting and standing at work did not experience increased mortality risks. Additionally, engaging in 15 to 30 minutes more of leisure-time physical activity (LTPA) per day or achieving a personal activity intelligence (PAI) score above 100 could reduce the elevated mortality risks associated with prolonged occupational sitting. The findings suggest that reducing prolonged sitting and increasing physical activity can significantly mitigate the health risks associated with occupational sitting.This study investigates the health risks associated with prolonged occupational sitting and whether there is a threshold of physical activity that can mitigate these risks. The research, conducted in Taiwan, followed 481,688 participants over a mean period of 12.85 years. The study found that individuals who predominantly sat at work had a 16% higher risk of all-cause mortality and a 34% higher risk of cardiovascular disease (CVD) mortality compared to those who predominantly did not sit at work. However, individuals who alternated between sitting and standing at work did not experience increased mortality risks. Additionally, engaging in 15 to 30 minutes more of leisure-time physical activity (LTPA) per day or achieving a personal activity intelligence (PAI) score above 100 could reduce the elevated mortality risks associated with prolonged occupational sitting. The findings suggest that reducing prolonged sitting and increasing physical activity can significantly mitigate the health risks associated with occupational sitting.