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 [removed].