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OBJECTIVE To describe the effect of a mesotherapy protocol in dogs with osteoarthritis. ANIMALS 30 dogs. PROCEDURES Dogs were randomly assigned to a control (CG; n = 10) or a mesotherapy group (MG; 20). CG received meloxicam for 70 days. MG was treated with a combination of lidocaine, piroxicam, and thiocolchicoside, injected in intradermal points. Seven treatment sessions were conducted. Response to treatment was measured with different instruments: the Canine Brief Pain Inventory (divided into Pain Interference Score [PIS] and Pain Severity Score [PSS]), Liverpool Osteoarthritis in Dogs (LOAD), and Canine Orthopedic Index (COI; divided into function, gait, stiffness, and quality of life), at time 0 (T0), +15 days, +30 days, +60 days, and +90 days after T0. At each time point, the results of the 2 groups with each instrument were analyzed with the Wilcoxon signed ranks test, P < .05. Kaplan-Meier estimators were compared with the Breslow test. RESULTS Dogs had a mean age of 6.9 ± 2.7 years and a body weight of 31.0 ± 6.4 kg. Hip osteoarthritis was classified as mild (n = 9), moderate (17), or severe (4). No differences were found at T0. Better results were observed in MG at +15 days (P < .01 for PSS and PIS, P = .03 for function), +30 days (P = .01 for PIS and LOAD, P = .03 for PSS, and P = .04 for function, gait, and COI), +60 days (P < .01 for PSS and PIS, P = .01 for LOAD, and P = .02 for function), and +90 days (P = .01 for PSS and PIS, P = .03 for LOAD, and P = .04 for function). Kaplan-Meier estimators showed MG had longer periods with better results than CG in various scores. CLINICAL RELEVANCE This mesotherapy protocol reduced pain scores and other clinical metrology instrument scores lasting for longer periods.