Background: To determine the incidence and risk factors of post-phototherapy rebound hyperbilirubinemia because data about bilirubin rebound in neonates are lacking and few studies have concerned this condition.

Methods: A prospective observational study was conducted on 500 neonates with indirect hyperbilirubinemia who were treated according to standard guidelines. Total serum bilirubin (TSB) was measured at 24-36 h after phototherapy; significant bilirubin rebound (SBR) is considered as increasing TSB that needs reinstitution of phototherapy.

Results: A total of 124 (24.9%) neonates developed SBR with TSB increased by 3.4 (2.4-11.2) mg/dL after stopping phototherapy. Multiple logistic regression model revealed the following significant risk factors for rebound: low birth weight (B = 1.3, P < 0.001, OR 3.5), suspected sepsis (B = 2.5, P < 0.001, OR 12.6), exposure to intensive phototherapy (B = 0.83, P = 0.03, OR 2.3), hemolysis (B = 1.2, P < 0.001, OR 3.1), high discharge bilirubin level (B = 0.3, P = 0.001, OR 1.3), and short duration of conventional phototherapy (B = − 1.2, P < 0.001, OR 0.3).