Background Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors primarily used for treatment of hyperlipidemia. Recently, they have been shown to inhibit proliferation of uterine fibroid cells and inhibit tumor growth in fibroid animal models. Objective We sought to examine the association between statin use and the risk of uterine fibroids and fibroid-related symptoms in a nationally representative sample of commercially insured women diagnosed with hyperlipidemia. Study Design We performed a nested case-control study of >190,000 women enrolled in one of the nation's largest commercial health insurance programs. From a cohort of women aged 18-65 years diagnosed with hyperlipidemia from January 2004 through March 2011, we identified 47,713 cases (women diagnosed with uterine fibroids) and 143,139 controls (women without uterine fibroids) matched at a 1:3 ratio on event/index date (month and year) and age (±1 year). We used conditional and unconditional logistic regression to calculate odds ratios and 95% confidence intervals for the risk of uterine fibroids and fibroid-related symptoms associated with prior use of statins. Results Exposure to statins within 2 years before the event/index date was associated with a decreased risk of uterine fibroids (odds ratio, 0.85; 95% confidence interval, 0.83–0.87). In a separate subanalysis restricted to cases, statin users had a lower likelihood of having menorrhagia (odds ratio, 0.88; 95% confidence interval, 0.84–0.91), anemia (odds ratio, 0.84; 95% confidence interval, 0.79–0.88), or pelvic pain (odds ratio, 0.85; 95% confidence interval, 0.81–0.91) and of undergoing myomectomy (odds ratio, 0.76; 95% confidence interval, 0.66–0.87) compared to nonusers. Conclusion The use of statins was associated with a lower risk of uterine fibroids and fibroid-related symptoms. Further studies, including randomized controlled trials, may be warranted.