OBJECTIVE To describe clinical findings and diagnostic test results and identify potential prognostic indicators for calves with septic arthritis. DESIGN Retrospective case series. ANIMALS 64 calves with septic arthritis. PROCEDURES The medical record database for a veterinary teaching hospital was searched to identify calves ≤ 6 months old that were treated for septic arthritis between 2009 and 2014. Data evaluated included signalment, history, physical examination and diagnostic test results, treatment, and outcome. Descriptive data were generated, and calves were assigned to 2 groups (neonatal [≤ 28 days old] or postneonatal [29 to 180 days old]) on the basis of age at hospital admission for comparison purposes. RESULTS 64 calves had 92 infected joints; 17 calves had polyarthritis. Carpal joints were most frequently affected followed by the stifle and tarsal joints. Forty-nine bacterial isolates were identified from synovial specimens for 38 calves, and the most commonly identified isolates were catalase-negative Streptococcus spp (n = 14) and Mycoplasma bovis (9). Calves in the neonatal group had a shorter interval between onset of clinical signs and hospitalization and were more likely to have an infected carpal joint than calves in the postneonatal group. Outcome was positive for 35 calves. Synovial fluid total nucleated cell count was positively associated with a positive outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that empirical antimicrobial treatment for calves with septic arthritis should target gram-positive catalase-negative cocci and M bovis and that synovial fluid total nucleated cell count might be a useful prognostic indicator.