Several risk factors for osteoporotic fractures have been identified but reports of the association of lipid parameters with the occurrence of osteoporotic fractures have been limited. We aimed to examine whether serum total cholesterol (TC) variability is associated with osteoporotic fractures. The study included 3,00,326 subjects who had undergone three or more health examinations between 2003 and 2008. The primary endpoint was the incidence of osteoporotic fractures, including vertebral, hip, distal radius, and humerus fractures. TC variability was evaluated based on the following three parameters: coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). A total of 29,044 osteoporotic fracture events (9.67%) were identified during a median of 11.6 years of follow-up. The risk of osteoporotic fractures in the highest quartile was significantly higher compared with the lowest quartile according to the three indices of TC variability with adjusted hazard ratios (HR) and 95% confidence intervals (CI) as follows: CV (HR 1.11, 95% CI [1.08–1.15]), SD (HR 1.07, 95% CI [1.04–1.11]) and VIM (HR 1.07, 95% CI [1.04–1.11]). The Kaplan–Meier curves showed a significantly positive relationship between the higher quartile of TC variability and overall osteoporotic fractures. The association remained significant in subgroup analyses of vertebral and hip fractures, regardless of the indices of TC variability. Our study showed that visit-to-visit TC variability was found to be associated with osteoporotic fracture risk. Maintaining TC levels stable may help attenuate the osteoporotic fracture risk in the future.