Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer‐bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057–1.479 and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127–6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer.