Physical activity (PA) is one of the most important modifiable factors associated with fracture risk. However, the association between interval changes in PA and the risk of fracture remains unknown. We investigated the risk of fracture development according to interval changes in PA in middle aged and older individuals. In this nationwide cohort study of adults aged ≥ 40 years, more than 4.9 million individuals without fractures within the last year who underwent two consecutive national health screenings in Korea from 2009 to 2012 were identified. The risk of fracture between 2013 and 2016 according to interval changes in regular PA was prospectively analyzed. Compared to individuals with a continuous lack of PA, those with a decrease in PA (0.41/1000 person-years (PY) decrease in incidence rate (IR); adjusted hazard ratio (aHR) 0.975; 95% confidence interval (CI) 0.964-0.987), increase in PA (1.8/1000 PY decrease in IR; aHR 0.948; 95% CI 0.937-0.959), and continuous PA (3.58/1000 PY decrease in IR; aHR 0.888; 95% CI 0.875-0.901) had a significantly reduced risk of fracture. Interval changes in regular PA were associated with risk of fracture. Individuals who engaged in continuous regular PA exhibited the maximum protective benefit against fracture.