Seventy dogs were included in a randomized, controlled, multicenter trial to test the efficacy of carprofen (2.2 mg/kg of body weight, PO, q 12 h) for relief of clinical signs associated with osteoarthritis. Thirty-six dogs received carprofen, and 34 received a placebo. Response of the dogs was evaluated by comparing results of force plate examination and a graded lameness examination performed before and immediately after 2 weeks of treatment, and by obtaining a subjective assessment of the dog's posttreatment condition from owners and participating veterinarians. A physical examination, CBC, serum biochemical analyses, urinalysis, and fecal occult blood test were performed before and after treatment to monitor safety. For force plate evaluation, the odds ratio was 3.3, meaning that a dog treated with carprofen was 3.3 times more likely to have a positive response than was a dog treated with the placebo. For evaluation by a veterinarian, the odds ratio was 3.5, and for owner evaluation, the odds ratio was 4.2. Institution where dogs were treated did not have a significant effect on results. A variety of reactions that may have been related to the medication (placebo or carprofen) were recorded; however, none were considered serious. Serum alanine aminotransferase activity was high in 3 dogs (2 that received placebo and 1 that received carprofen) at the conclusion of treatment; none of the 3 dogs were clinically ill. Ten dogs (5 that received placebo and 5 that received caprofen) had negative pretreatment and positive posttreatment fecal occult blood test results.