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Simple Summary: Racing provides employment and career engagement, is passionately pursued, and helps sustain our close relationship with horses, but it can also be associated with injury and losses. Fatalities occur on and off racetracks, involving welfare concerns, economic impact, and damage to racing's public profile and social license. Musculoskeletal injury, the most visible loss, represents only one source and remains poorly understood, while for other losses and off-track mortality little is known. In 2003, the Province of Ontario, Canada introduced a registry for racehorse mortalities, providing opportunities to better understand losses and contributing factors. Following an earlier publication describing losses across all breeds, this paper presents analysis of standardbred mortality and relationships with routine management and competition. Results reveal that aspects of industry structure may contribute to mortality, and that the impact might be anticipated by close monitoring of a horse's profile and performance. The immediate circumstances precipitating any specific fatality should be seen as separate from this underlying environmental liability. This has implications for how future research might be conducted and findings interpreted. It is hoped the present study can be used to decrease mortality and cumulative injury so as to reduce losses and strengthen societal support for racing. Factors associated with mortality in standardbred racehorses were assessed through a retrospective annualized cohort study of all-cause mortality from 2003–2015 (n = 978) (identified in the Ontario Racehorse Death Registry). Race and qualifying data for official work-events were also gathered (1,778,330 work-events, 125,200 horse years). Multivariable logistic regression analysis revealed sex, age, and indices of workload and intensity and their interactions to be strongly associated with mortality. Track class, race versus qualifying performance, and work-event outcome (finish position, scratched, or failed to finish) also influenced mortality odds, which increased as performance slowed. Intense competition at higher performance levels and qualifying races at lower levels carried particularly high odds. Though occurring frequently, musculoskeletal injury was less frequent than all other presenting problems combined. Industry structure contributes to mortality through interaction between horse characteristics and the competition environment. This substrate may be amenable to management to minimize liability, but incident-specific triggers may represent chance factors and be relatively difficult to identify or control. Differentiating between substrate and trigger when studying specific clinical problems may provide greater clarity and yield in identifying underlying causes. Mortality may reflect a continuum of circumstances, cumulative impacts of which might be identified before a fatal event occurs. [ABSTRACT FROM AUTHOR]