OBJECTIVE: To identify risk factors for development of excessive tibial plateau angle (TPA) in large-breed dogs with cranial cruciate ligament disease (CCLD). DESIGN: Case-control study. ANIMALS: 58 dogs with excessive TPAs (ie, TPA >or= 35 degrees ; case dogs) and 58 dogs with normal TPAs (ie, TPA <or= 30 degrees ; control dogs). PROCEDURES: Medical records and radiographs were reviewed and owners were interviewed to identify potential risk factors for excessive TPA. RESULTS: Case dogs were 3 times (95% confidence interval, 1.2 to 8.0) as likely to have been neutered before 6 months of age as were control dogs. Case dogs with TPA >or= 35 degrees in both limbs were 13.6 times (95% confidence interval, 2.72 to 68.1) as likely to have been neutered before 6 months of age as were control dogs with TPA <or= 30 degrees in both limbs. Case dogs were significantly younger at the onset of hind limb lameness than were control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that early neutering was a significant risk factor for development of excessive TPA in large-breed dogs with CCLD. Further research into the effects of early neutering on TPA and the pathophysiology of CCLD is warranted.