Lameness continues to cause significant problems in profitability, productivity, and animal welfare in the feedlot industry. Toe tip necrosis syndrome (TTNS) is a new name for a previously reported condition. By definition, TTNS is separation of the apical white line with tissue necrosis and clinical lameness. This definition includes complications such as pedal (P3) osteitis, middle (P2) and proximal (P1) phalangeal osteomyelitis, tendonitis, tenosynovitis, cellulitis, and embolic pneumonia. Anecdotal experiences from practitioners report this lameness in feedlot cattle will develop within weeks after feedlot entry. Often the hindlimbs, specifically the lateral claw, are affected where a separation of the dorsal wall and sole will be noticed. Secondary infections will progress deeper into the foot and become systemic. Unfortunately, despite treatment, these animals can become very lame and will need to be euthanized. The overall objective of this project was to describe the epidemiology of TTNS in western Canadian feedlot cattle. The specific objectives were 1) to use clinical examinations, imaging modalities, and necropsy findings to aid in description, classification, and characterization of TTNS lesions, 2) to describe the epidemiology of TTNS in feedlot cattle, and 3) to evaluate risk factors for TTNS. Upon further investigation into this arrival related condition it became apparent that there were many different descriptors: P3 necrosis, toe abscess, apicus necrotica, apical pedal bone necrosis or toe necrosis. These names and descriptors of toe tip lesions were based on anecdotal experiences and previous case reports. As a result, traditional epidemiological approaches that included field investigations, clinical and necropsy examinations were implemented to identify, characterize and describe this condition. Based on clinical findings, imaging modalities, and necropsy specimens examined during September to December 2012, inclusive, a more specific name and descriptive case definition were introduced. TTNS descriptive epidemiology was described by use of a retrospective database analysis from Feedlot Health Management Services (FHMS) with 702 veterinarian confirmed TTNS cases by necropsy examination. From this database, there were 30% (210/702) of necropsy cases treated for TTNS and 70% of cases (492/702) that were not treated. Of those animals treated, the mean and standard deviation (median) interval from feedlot arrival to first treatment was 18.9 ±1.7 d (12 d). The mean (standard deviation) days on feed until death from TTNS was the earliest in grass-fed calves (32.4 ± 22.1 d), followed by auction-derived (40.6 ± 40.6 d), ranch direct (44.1 ± 53.1 d), and back-grounded calves (69.0 ± 75.6 d) (P < 0.001). Yearlings were on feed for a mean (standard deviation) days of 37.1 ± 32.0 d when compared to calves at 49.5 ± 57.0 d before death (P < 0.001). The greatest proportion of deaths occurred from September to November. There were 96.2% (1,832/1,904) of lots without one case of TTNS and 3.8% (72/1,904) of lots had one or more TTNS cases. A prospective case-control study to identify TTNS risk factors consisted of 148 total necropsy submissions (82 cases, 66 controls) from three feedlot veterinary practices and 16 feedlots during October 2012 to January 2013, inclusive. Confirmation of feet samples by the principal investigator at the Western College of Veterinary Medicine reduced the total to 135 animals: 67 cases and 68 controls. The measure of agreement (kappa) on classification of TTNS cases and controls between the veterinary practice and WCVM was 0.778 (P < 0.001). Bacterial culture results revealed that 75% of pure isolates in TTNS cases were attributed to Escherichia coli, Streptococcus spp., Trueperella pyogenes, Fusobacterium necrophorum. TTNS cases were 3.8 times more likely than control animals to have BVDV isolated (95% CI 1.7-8.5; P < 0.001). TTNS animals were 2.2 times more likely than control animals to have histopathological evidence of vasculitis (95% CI 1.0-4.6; P = 0.04). BVDV samples were 11.2 times more likely to show histopathological evidence of vasculitis than non-BVDV samples (95% CI 4.7-27.0; P < 0.001). A decreased difference was found in sole thickness at the toe tip (P < 0.001). There was no evidence of pedal bone rotation between case and control animals (P = 0.15). In summary, TTNS is a specific term for apical white line separation with tissue necrosis and clinical lameness. A practitioner's field diagnosis of TTNS based on apical white line separation and tissue necrosis is accurate on clinical signs alone. TTNS is a transport or arrival related condition in feedlot cattle that has a propensity for cases to cluster together. Pure bacterial isolates provide an understanding of the pathogens responsible for TTNS and that environmental pathogens contribute to an ascending infection. BVDV, vasculitis and apical sole thickness were risk factors associated with TTNS; however, their exact role requires further investigation.