Nonsteroidal anti-inflammatory drugs (NSAIDs) have been commonly used to treat endodontic post-operative pain. The purpose of this study was to address the Population, Intervention, Comparator, Outcome, Timing, Study design and setting (PICOTS) question: in patients with pre-operative pain who undergo initial orthograde endodontic treatment, what is the comparative efficacy of NSAIDS compared to placebo or non-narcotic analgesics in reducing post-operative pain and incidence of adverse events?