BACKGROUND: There are four routinely prescribed classes of medications to treat inflammatory bowel disease (IBD): aminosalicylates (balsalazide, mesalamine, olsalazine, sulfasalazine), corticosteroids (budesonide, methylprednisolone, prednisone, prednisolone), immunomodulators (6-mercaptopurine, azathioprine, cyclosporine, methotrexate), and biologics (TNF-alpha antagonists [adalimumab, certolizumab, golimumab, and infliximab] and integrin receptor antagonists [natalizumab and vedolizumab]). Many patients worry about the safety of these medications as all classes except aminosalicylates carry warnings for serious adverse events on the Food & Drug Administration (FDA) labels. The biologic medications are of special concern due to media attention related to fatal cancers associated with use, particularly in boys and young men. We aimed to compare serious adverse events for biologics and other IBD medications with all other FDA-approved medications using adverse events reported to the FDA Adverse Event Reporting System (FAERS). We limited our primary analyses to medications associated with an IBD indication. METHODS: We queried FAERS for serious adverse events (SAE) using Empirica Signal (Oracle Corp., Redwood Shores, CA) based on reports made to the FDA between January 1998 and March 2017. We customized our disproportionality analysis to calculate and compare the cumulative EB05 values for serious adverse events of all IBD medications since their dates of approval. An EB05 value of 2 indicates that a medication-event frequency is double that of other medication-event pairs in the FAERS database (the EB05 is the lower confidence limit of a Bayesian disproportionality measure). We examined the SAE that are most common and carry the highest EB05 signals for each biologic. Lastly, we compared safety signals of IBD biologics indicated for a gastrointestinal indication versus all other indications. Gastrointestinal indications were selected by using Medical Dictionary for Regulatory Activities (MedDRA), a standardized dictionary of adverse events. RESULTS: From our analysis comparing cumulative EB05 values of SAE associated with a biologic with the indication of IBD to all other serious adverse events reported to FAERS, infliximab had the highest EB05 signal of 1.53. Adalimumab had the lowest cumulative EB05 value of 0.58. The cumulative EB05 values of corticosteroids, immunomodulators, and aminosalicylates were 1.0, 1.19, and 0.92, respectively. The majority of SAE were gastrointestinal and were present for biologics and other treatment classes. Relaxing the inclusion criteria to include a gastrointestinal indication, instead of an IBD indication, and allowing all indications (including rheumatoid arthritis) resulted in higher EB05 values. The highest cumulative EB05 values were observed for infliximab, vedolizumab, and immunomodulators. The highest safety signal associated with any IBD biologic treatment that was not a known complication of IBD or already listed on the label was listeria meningitis (EB05 38.05) which was only elevated for infliximab. Clostridium difficile (EB05 26.67) was the second highest safety signal and was seen with golimumab. CONCLUSION(S): Medications to treat IBD, including biologics, are as safe as all other FDA-approved drugs. There was no safety signal associated with any biologic to treat IBD associated with serious adverse events in general. We identified new serious adverse events that were not previously listed on the safety labels of biologics.