The published, peer-reviewed literature was systematically searched for information on the safety and efficacy of long-term (defined as 28 days or more of continuous therapy) NSAID use in the treatment of canine osteoarthritis. Online databases were reviewed in June 2008 and papers were selected based on their relevance. Fifteen papers were identified and evaluated. Six of seven papers indicated a benefit of long-term treatment over short-term treatment in terms of the reduction of clinical signs or lameness; one study showed no benefit. Fourteen papers evaluated safety with calculated experimental (adverse) event rates (EER) between 0 and 0.31, but there was no correlation between study length and EER (rs=-0.109, P=0.793). The balance of evidence for the efficacy of NSAIDs supports longer-term use of these agents for increased clinical effect. There is no indication in the literature that such an approach is associated with a reduction in safety, although robust data on the safety of long-term NSAID use are lacking in large numbers of dogs.