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While knee injuries are treated by a wide range of clinicians, patients with knee injuries frequently present to emergency departments (EDs). The knee is the most commonly injured joint by adolescent athletes with an estimated 2.5 million sports-related injuries presenting to EDs annually.The objective was to examine the epidemiology of knee injuries presenting to EDs in the United States from 1999 through 2008.The Consumer Product Safety Commission National Electronic Injury Surveillance System database (NEISS) was used to examine causes of knee injuries treated in U.S. EDs from 1999 through 2008.An estimated 6,664,324 knee injuries presented to U.S. EDs from 1999 through 2008, for a rate of 2.29 knee injuries per 1,000 population. Those 15 to 24 years of age had the highest injury rate (3.83), while children younger than 5 years had the lowest rate (0.55). The most common diagnoses were strains and sprains (42.1%), contusions and abrasions (27.1%), and lacerations and punctures (10.5%). The most common general product categories causing injury were sports and recreation (49.3%), home structures (30.2%), and home furnishings (13.6%). Several sex and age group differences were identified. For example, males sustained a higher proportion of basketball-related injuries (11.1%) than females (3.6%; injury proportion ratio [IPR] = 3.11, 95% confidence interval [CI] = 2.79 to 3.46, p < 0.001). Additionally, individuals 65 years and older sustained a higher proportion of injury due to stairs, ramps, landings, and floors (42.0%), compared to all other ages (20.1%; IPR = 2.09, 95% CI = 1.95 to 2.23, p < 0.001).Rates and patterns of knee injuries vary by sex and age. Although knee injuries will likely continue to occur most frequently among youth and young adult athletes, anticipating and responding to trends such as an increase in the incidence of knee injuries among adult and senior patients will enable clinicians to better anticipate caseloads, allocate resources, and determine best practices for diagnosis and treatment of knee injuries in different age groups.