Cyclo-oxygenase enzymes and prostaglandins have long been known to have a role in tumor growth and promotion. Piroxicam has been found to be effective against several types of neoplasms and is often prescribed for chronic use. There have been no studies evaluating chronic piroxicam administration in cats and the chronic use of non-steroidal anti-inflammatory agents such as piroxicam has been discouraged in cats. Seventy-three cats were included in this retrospective study. Piroxicam was the sole therapy in 28 cats (38%). Piroxicam with various chemotherapeutic agents was administered to 25 cats and 20 cats had piroxicam with radiation therapy. The main adverse reaction noted was an increase in vomiting during the first month of therapy that was most significant in cats receiving concurrent chemotherapy. The chronic administration of piroxicam was not significantly associated with hematologic, renal, or hepatic toxicities. The occurrence of azotemia several months after initiating therapy in three cats emphasizes the need to monitor renal values in cats receiving piroxicam. Those cats with renal azotemia prior to starting piroxicam did not appear to have evidence of progressive azotemia while receiving the drug. Adverse events were reported in 29% of cats, and were generally mild and transient. This study found low toxicity with chronic use of piroxicam in cats, though future studies are needed to evaluate the clinical efficacy, effective dose, and anti-neoplastic mechanisms of piroxicam. [VT]