Objective To systematically review and synthesize the evidence on physical activity and sedentary behavior after serious orthopedic injury. Data Sources Eight electronic databases and reference lists of relevant articles were searched from inception to March 2016. Study Selection Studies on physical activity and sedentary behavior measured objectively or via self-report among patients with a serious orthopedic injury (acute bone or soft tissue injury requiring emergency hospital admission and/or nonelective surgery) were included. Data Extraction Data extraction and methodological quality assessment were independently performed by 2 reviewers using standardized checklists. Data Synthesis Twelve of 2572 studies were included: 8 were on hip fractures and 4 on other orthopedic injuries. Follow-up ranged from 4 days to 2 years postinjury. When measured objectively, physical activity levels were low at all time points postinjury, with individuals with hip fracture achieving only 1% of recommended physical activity levels 7 months postinjury. Studies using objective measures also showed patients to be highly sedentary throughout all stages of recovery, spending 76% to 99% of the day sitting or reclining. For studies using self-report measures, no consistent trends were observed in postinjury physical activity or sedentary behavior. Conclusions For studies using objective measures, low physical activity levels and high levels of sedentary behaviors were found consistently after injury. More research is needed not only on the impact of immobility on long-term orthopedic injury outcomes and the risk of chronic disease, but also the potential for increasing physical activity and reducing sedentary behavior in this population.