The purpose of this review is to define the toleration profile of piroxicam through the clinical experience gathered in 109,495 patients and to estimate how it compares with that of other commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) in 37 comparative clinical trials involving 3,580 patients. The estimated total exposure to piroxicam in clinical trials reported here is approximately 2.6 million patient days. The toleration profile of piroxicam is typical of an inhibitor of prostaglandins, with a relatively low reported incidence of adverse events necessitating discontinuation of therapy. Pharmacokinetics are not age- or sex-dependent, and - with the exception of oedema - the incidence of adverse events does not increase with age. Piroxicam exhibits better toleration than indomethacin (75 to 150 mg daily), naproxen (1,000 mg daily), and enteric coated acetylsalicylic acid (3.5 to 5 g daily), and is as well tolerated as diclofenac (75 to 150 mg daily), naproxen (500 to 750 mg daily), and ibuprofen (2.4 g daily). Piroxicam has the advantage that once-daily dosage is sufficient to provide efficacy equal to or better than these comparative agents.