Use of force (UOF) by police can result in serious injuries and fatalities; however, the risk of significant injuries associated with different force modalities is poorly defined. The authors sought to determine the incidence of police UOF and compare the likelihood of significant injury with different force modalities. The authors conducted a prospective multicenter observational study of all UOF incidents at three mid-sized police agencies over a two-year period. Expert physicians reviewed police and medical records to determine injury severity using a priori injury severity stratification criteria. The research findings conclude that police UOF, and resulting significant injuries, are rare. When force is used, officers most commonly rely on unarmed physical force and conducted electrical weapons (CEWs). The results reveal 893 UOF incidents, representing a UOF rate of 0.086% of 1,041,737 calls for service (1 in 1167) and 0.78% of 114,064 criminal arrests (1 in 128). Suspects were primarily young (mean age, 31 years; range, 12–86 years) males (89%). The 1,399 force utilizations included unarmed physical force (n = 710, 51%), CEWs (504, 30%), chemical (88, 6.3%), canines (47, 3.4%), impact weapons (9, 0.6%), kinetic impact munitions (8, 0.6%), firearms (6, 0.4%), and other (27, 1.9%). Among 914 suspects, 898 (98%) sustained no or mild injury after police UOF. Significant injuries, mostly associated with firearm and/or canine use, occurred in 16 (1.8%) subjects. There was one fatality (0.1%) due to gunshots. No significant injuries occurred among 504 CEW uses (0%; 95% confidence interval, 0.0–0.9%). Of the 355 suspects transported to a medical facility, 78 (22%) were hospitalized. The majority of hospitalizations were unrelated to UOF (n = 59, 76%), whereas a minority (n = 19, 24%) were due to injuries related to police UOF.