Background: Social media may complement traditional data sources to answer comparative effectiveness/safety questions after medication licensure. Methods: The Treato platform was used to analyze all publicly available social media data including Facebook, blogs, and discussion boards for posts mentioning inflammatory arthritis (e.g. rheumatoid, psoriatic). Safety events were self-reported by patients and mapped to medical ontologies, resolving synonyms. Disease and symptom-related treatment indications were manually redacted. The units of analysis were unique terms in posts. Pre-specified conditions (e.g. herpes zoster (HZ)) were selected based upon safety signals from clinical trials and reported as pairwise odds ratios (ORs); drugs were compared with Fisher's exact test. Empirically identified events were analyzed using disproportionality analysis and reported as relative reporting ratios (RRRs). The accuracy of a natural language processing (NLP) classifier to identify cases of shingles associated with arthritis medications was assessed. Results: As of October 2015, there were 785,656 arthritis-related posts. Posts were predominantly US posts (75%) from patient authors (87%) under 40 years of age (61%). For HZ posts (n815), ORs were significantly increased with tofacitinib versus other rheumatoid arthritis therapies. ORs for mentions of perforated bowel (n=13) were higher with tocilizumab versus other therapies. RRRs associated with tofacitinib were highest in conditions related to baldness and hair regrowth, infections and cancer. The NLP classifier had a positive predictive value of 91% to identify HZ. There was a threefold increase in posts following television direct-to-consumer advertisement (p=0.04); posts expressing medication safety concerns were significantly more frequent than favorable posts. Conclusion: Social media is a challenging yet promising data source that may complement traditional approaches for comparative effectiveness research for new medications.