Although case reports of a possible association between statin therapy and tendon rupture have been published, no analytical studies exploring this relationship have been reported. We conducted a case-control study using the electronic medical records at Michigan State University from 2002 to 2007 to assess whether statin use is a risk factor for tendon rupture. We compared exposure to statins in 93 cases of tendon rupture with similar exposure in 279 sex- and age-matched controls. Exposure to statins was defined as documentation in the electronic medical record of statin use in the 12 months preceding tendon rupture. For controls, the exposure period was defined as 1 year preceding the last office visit. We used a multivariate logistic regression model, controlling for diabetes, renal disease, rheumatologic disease, and steroid use, to calculate the adjusted odds ratios (ORs). There was no significant difference between cases and controls in the rates of statin use, with either univariate [OR = 1.0, 95% confidence interval (CI) 0.54-1.84] or multivariate analyses (OR = 1.10, 95% CI 0.57-2.13). Based on predetermined subgroup analyses, statin exposure was found to be a significant risk factor for tendon rupture in women (adjusted OR = 3.76, 95% CI 1.11-12.75) but not in men (adjusted OR = 0.66, 95% CI 0.29-1.51). In conclusion, we found no overall association between statin use and tendon rupture, but subgroup analysis suggested that women with tendon rupture were more likely to be on statins.