Cephalohematoma is a common pathology in newborns. Observation is the primary treatment for most patients with small uncomplicated cephalohematoma. Conversely, a large cephalohematoma can lead to calcification with unesthetic local deformation or deformational plagiocephaly. The objective of the study was to evaluate the iatrogenic risk associated with early puncture under local anesthesia and oral sucrose. This is a retrospective study of 67 consecutive newborns followed at Montpellier University Hospital, France, between 2010 and 2017. Large cephalohematoma was defined on the basis of the bump projection. Due to the uncertainty of the spontaneous resorption and the risk of calcification after 4 weeks which render the needle aspiration ineffective, puncture was performed between 2 and 4 weeks of life after coagulation evaluation and ultrasound of the skull and scalp. Puncture was performed in 43 boys (64%) and 24 (36%) girls between day 15 and day 30 after birth. The cephalohematoma maximal projection measured by ultrasound ranged from 9 to 13 mm (Q1,Q4) with a median value of 12 mm. No puncture-related complication was recorded during the intervention and at the 1-month follow-up visit.Conclusion: In newborns with large and persistent unesthetic cephalohematoma, puncture under local anesthesia with oral sucrose can be safely proposed between day 15 and day 30 after birth.What is Known:• Infant cephalohematoma is a frequent pathology of newborns, consisting of a traumatic subperiosteal hematoma of the skull. Most cephalohematomas are small and require no treatment because they spontaneously disappear within the first month.• Large and non-resorptive cephalohematomas may have significant esthetic and functional consequences.What is New:• Early puncture under local anesthesia is a safe, effective, and rapid procedure, decreasing the risk of persistent skull deformities.• Puncture can be proposed for newborns with a large (high projection and/or high angle connection) persistent anesthetic cephalohematoma, between day 15 and day 30, before spontaneous calcification.