Background: Prior studies suggest that medication exposures may be associated with new onset inflammatory bowel disease (IBD). The aim of this study was to determine the effect of specific medication classes on the risk of new onset IBD in a large United States health claims database. Methods: We conducted a matched case-control study with a national medical claims and pharmacy database from Source Healthcare Analytics LLC (SHA). This database included any patient age 18 or older with ICD-9 code 555.x for Crohn's disease (CD) or 556.x for ulcerative colitis (UC) between January 2008 and December 2012. Each IBD patient had up to 10 age, gender, race, and state matched controls using propensity scoring. Controls had no ICD-9 codes for CD, UC or IBD-associated diseases and no prescriptions for IBD-related medications. 12,544,273 patients were included in the database. New onset IBD patients were defined as having at least 3 separate CD or UC ICD-9 codes and at least 1 year with no IBD-related ICD-9 or prescription prior to index IBD ICD-9. 92,933 new IBD cases were matched with 929,330 controls. For this first analysis, we examined drug classes previously shown to modify established IBD or affect risk of new onset IBD. Drug class was defined by Uniform System of Classification (USC) level 5 code. To account for diagnostic delay, exposures within 6 months of index ICD-9 were excluded. Conditional logistic regression was used to identify medications associated with new onset IBD, CD, and UC. The Benjamini-Hochberg correction was applied to control the type I error rate at the 5% significance level. Results: Estimated odds ratios (OR) and 95% confidence intervals (CI) for new onset IBD, CD, and UC for medication classes of interest are shown in Table 1. Most classes of antibiotics were associated with an increased risk of IBD. The most strongly associated antibiotic classes were trichomonacides which include metronidazole and tinidazole and a USC 5 class which includes metronidazole as well as imipenam, ertapenam, polymyxin, and vancomycin. Prescriptions with estrogen alone were associated with an increased risk of IBD. However, progesterone or estrogen-progesterone combinations either had no association or demonstrated a protective effect against new IBD. Acne agents that do not contain anti-infectives, including isotretinoin, benzoyl peroxide, salicylic acid and tretinoin, did not increase the risk of IBD. The strongest protective effect against new onset IBD, and especially CD, was seen with statins. Conclusions: To our knowledge, this is the first study to suggest a protective effect of statins against new onset IBD. We also replicate prior findings that most antibiotics and estrogens are associated with new IBD. The acne medication class containing isotretinoin did not increase the risk of IBD. These findings should be confirmed in future studies. Table 1: Representative list of medication classes of interest with ORs for new onset IBD, CD, and UC