Clinicians cannot reliably predict complications of acute hematogenous osteomyelitis (AHO). Consecutive cases of AHO from 2 pediatric centers in the United States were analyzed retrospectively to develop clinical tools from data obtained within 96 hours of hospitalization to predict acute and chronic complications of AHO. Two novel composite prediction scores derived from multivariable logistic regression modeling were compared with a previously published severity of illness (SOI) score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using area under the receiver operating characteristic curve analyses. The causative organisms were identified in 73% of 261 cases. Bacteremia (45%), abscesses (38%), and associated suppurative arthritis (23%) were relatively common. Acute or chronic complications occurred in 24% and 11% of patients, respectively. Multivariable logistic regression identified bone abscess (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0-5.2]), fever > 48 hours (OR, 2.7 [95% CI, 1.2-6.0]), suppurative arthritis (OR, 3.2 [95% CI, 1.3-7.5]), disseminated disease (OR, 4.6 [95% CI, 1.5-14.3]), and delayed source control (OR, 5.1 [95% CI, 1.4-19.0]) as strong predictors of acute complications. In a separate model, CRP ≥ 100 mg/L at 2-4 days after antibiotics (OR, 2.7 [95% CI, 1.0-7.3]), disseminated disease (OR, 3.3 [95% CI, 1.1-10.0]), and requirement for bone debridement (OR, 6.7 [95% CI, 2.1-21.0]) strongly predicted chronic morbidity. These variables were combined to create weighted composite prediction scores for acute (A-SCORE) and chronic (C-SCORE) osteomyelitis, which were superior to SOI, CRP, and ESR and had negative predictive values > 90%. Two novel composite clinical scores were superior to existing tools to predict complications of pediatric AHO.