To investigate risk factors associated with cranial cruciate ligament rupture in dogs. Retrospective case-control study: medical records of a first-opinion veterinary practice were searched for dogs diagnosed with cranial cruciate ligament rupture (1995 to 2007). For each case, six unaffected dogs were randomly selected from all dogs presenting that day for comparison. Multi-variable binary logistic regression was performed to assess the association of variables on likelihood of cruciate rupture. Frequency of cranial cruciate ligament rupture was 1·19% [95% confidence interval (CI) 1·02 to 1.36%]. West Highland white terriers (n=17), Yorkshire terriers (n=14) and Rottweilers (n=11) were at significantly increased risk of cranial cruciate ligament rupture (P≤0·002). Rottweilers were at five times greater risk compared with other pure breeds (OR 5·12, 95% CI 2·281 to 11·494, P<0·001), obesity quadrupled the risk of cranial cruciate ligament rupture (OR 3·756, 95% CI 1·659 to 8·502, P=0·001) and females were twice as likely to suffer cranial cruciate ligament failure compared to males (OR 2·054, 95% CI 1·467 to 2·877, P<0·001). Dogs less than two years old were statistically less likely to sustain cranial cruciate ligament rupture than dogs older than eight years (OR 0·246, 95% CI 0·127 to 0·477, P<0·001). There was no significant difference in median weights (in kilograms) of neutered dogs, compared to their entire counterparts in either the case group (P=0·994) or in the control group (P=0·630). There was also no significant difference in body condition (-underweight/normal weight/overweight/obese) of neutered versus entire dogs among the cases (P=0·243), or the controls (P=0·211). Cranial cruciate ligament rupture is more likely in Rottweilers and in female dogs, older dogs and obese dogs. Following multi-variable analysis, it was established that neutering was not associated with increased risk of cranial cruciate ligament rupture.