Statins have pleiotropic properties that may affect the development of connective tissue diseases (CTD). The objective of this study was to compare the risk of CTD diagnoses in statin users and nonusers. This study was a propensity score-matched analysis of adult patients (30 to 85 years old) in the San Antonio military medical community. The study was divided into baseline (October 1, 2003 to September 30, 2005), and follow-up (October 1, 2005 to March 5, 2010) periods. Statin users received a statin prescription during fiscal year 2005. Nonusers did not receive a statin at any time during the study. The outcome measure was the occurrence of 3 diagnosis codes of the International Classification of Diseases, 9th Revision, Clinical Modification consistent with CTD. We described co-morbidities during the baseline period using the Charlson Comorbidity Index. We created a propensity score based on 41 variables. We then matched statin users and nonusers 1:1, using a caliper of 0.001. Of 46,488 patients who met study criteria (13,640 statin users and 32,848 nonusers), we matched 6,956 pairs of statin users and nonusers. Matched groups were similar in terms of patient age, gender, incidence of co-morbidities, total Charlson Comorbidity Index, health care use, and medication use. The odds ratio for CTD was lower in statin users than nonusers (odds ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.05). Secondary analysis and sensitivity analysis confirmed these results. In conclusion, statin use was associated with a lower risk of CTD. Published by Elsevier Inc.Pharmac