Few epidemiological studies have investigated the relationship between work exposures and injury risk among custodians. The relationship between injury risk and occupational physical demands (e.g. pushing/pulling, lifting) and school environment characteristics (e.g. school type, season) was investigated among a cohort of 581 school custodians over a 4-year period. In the final Poisson regression models, the risk of injury was associated with time spent in pushing/pulling tasks in a dose-response manner increasing to a five-fold risk among the highest quartile of exposure (risk ratio = 5.15, 95% CI 1.00, 26.5). Injury risk was also associated with working during the school year compared to the summer, working in a school with grass vs. gravel grounds and working in a school with detached classrooms. Results help to target interventions such as alternative methods for floor cleaning to reduce the pushing/pulling demands of custodial work and to support decisions for alternatives to detached classrooms and grass surfaces. Statement of Relevance: This study examines ergonomic factors (physical demand exposures, school environment characteristics) associated with injury risk among custodial school workers. The findings help schools to target interventions to reduce the physical demands associated with injuries and to design school environments to reduce exposures.