Purpose: To investigate the association between obesity and work-site injury. Methods: Self-reported weight, height, and injuries within the previous three months were collected annually for US workers in the NHIS from 2004-2012. Participants were categorized as normal weight (BMI: 18.5 - <25 kg/m2), overweight (BMI: 25 - <30), obese I (BMI: 30 - <35), and obese II (BMI: =35). Prevalence ratios (PR) and 95% confidence intervals (CI) from the fitted logistic regression model were used to assess relationships between obesity and injury. Results: Compared to normal weight workers, overweight and obese workers were more likely to experience work-site injuries (overweight: PR=1.25, 95% CI=1.04-1.52; obese I: 1.41 (1.14-1.74); obese II: 1.68 (1.32-2.14). These injuries were more likely to affect the lower extremities (overweight: PR=1.48, 95% CI=1.03-2.13; obese I: 1.70 (1.13-2.55); obese II: 2.91 (1.91-4.41) and more likely to be due to sprains/strains/twists (overweight: 1.73 (1.29-2.31); obese I: 2.24 (1.64-3.06); obese II: 2.95 (2.04-4.26). Conclusion: Among NHIS participants, overweight and obese workers were 25% to 68% more likely to experience injuries than normal weight workers. Weight reduction policies and management programs may be effectively targeted towards overweight and obese groups to prevent or reduce work-site injuries.