The American Academy of Pediatrics provides little guidance on when to discontinue phototherapy in newborns treated for hyperbilirubinemia. We sought to develop a prediction rule to estimate the probability of rebound hyperbilirubinemia after inpatient phototherapy. Subjects for this retrospective cohort study were infants born in 2012 to 2014 at ≥35 weeks’ gestation at 16 Kaiser Permanente Northern California hospitals who received inpatient phototherapy before age 14 days. We defined rebound as the return of total serum bilirubin (TSB) to phototherapy threshold within 72 hours of phototherapy termination. We used stepwise logistic regression to select predictors of rebound hyperbilirubinemia and devised and validated a prediction score by using split sample validation. Of the 7048 infants treated with inpatient phototherapy, 4.6% had rebound hyperbilirubinemia. Our prediction score consisted of 3 variables: gestational age <38 weeks (adjusted odds ratio [aOR] 4.7; 95% confidence interval [CI], 3.0-7.3), younger age at phototherapy initiation (aOR 0.51 per day; 95% CI, 0.38-0.68), and TSB relative to the treatment threshold at phototherapy termination (aOR 1.5 per mg/dL; 95% CI, 1.4-1.7). The model performed well with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.86-0.91) in the derivation data set and 0.88 (95% CI, 0.86-0.90) in the validation data set. Approximately 70% of infants had scores <20, which correspond to a <4% probability of rebound hyperbilirubinemia. The risk of rebound hyperbilirubinemia can be quantified according to an infant's gestational age, age at phototherapy initiation, and TSB relative to the treatment threshold at phototherapy termination.