The epidemiology of pediatric acute osteomyelitis in the USA, such as annual hospitalization rates and disparities with respect to age, sex, race/ethnicity, and socioeconomic status, remains unknown. We obtained discharge records of hospitalized patients with acute osteomyelitis younger than 20 years of age from the Kids Inpatient Database for 2006, 2009, and 2012. We weighted the records to estimate the number of hospitalizations in the USA and calculated the annual rates of hospitalization because of acute osteomyelitis. We used a multivariable logistic regression analysis to assess the risk factors associated with the development of septic arthritis and bacteremia/septicemia. Overall annual hospitalization rates ranged from 1.34 to 1.66/100 000 children. Male-to-female ratios were 1.6−1.8. Black children, children aged 2, 7, and 12 years, and those living in very low median household income regions were more likely to have higher hospitalization rates. The lower limbs were the most frequent infection sites. Osteomyelitis at the pelvis/thigh, upper arm, hand, and forearm was significantly associated with the development of septic arthritis and bacteremia/septicemia. We determined the epidemiological patterns of pediatric acute osteomyelitis in the USA and identified the risk factors associated with the development of septic arthritis and bacteremia/septicemia. Level of Evidence: Level II.