ABSTRACT Vacuum-assisted vaginal delivery (VAVD) is used to expedite vaginal delivery in cases of an arrest of descent, maternal exhaustion, or concern for fetal well-being. In 2015, the rate of VAVD was greater than the use of forceps in the United States (2.58% vs 0.56%). Several studies have examined various characteristics of vacuum devices, such as cup shape and material, number of pulls, and number of pop-ups, which is defined as the spontaneous dislodgment of the cup from the fetal scalp. Vacuum manufacturers, such as Kiwi and Mityvac, recommend abandoning VAVD as an intervention after 2 or 3 pop-offs; however, the American College of Obstetricians and Gynecologists acknowledges that there are not enough data to recommend guidelines on how many pop-offs should be allowed before discontinuing. Some studies have demonstrated an increased risk of adverse neonatal outcomes with any number of pop-offs versus no pop-offs, whereas other studies have shown no independent association between the number of pop-offs and neonatal head injury. In addition, compared with an increase in the number of pop-offs, a large multicenter study found that increased duration of VAVD has a stronger association with adverse outcomes. The aim of this study was to examine the association between the number of pop-offs and adverse neonatal outcomes. This was a retrospective cohort study conducted at a single tertiary care institution from October 1, 2005, to June 1, 2014. Data were collected from electronic medical records. Included were adult women with singleton pregnancies who delivered via VAVD or a trial of VAVD followed by cesarean delivery. Excluded were those who underwent sequential trials of both vacuum and forceps. Institutional policy recommended converting to cesarean delivery after >3 pop-offs, but the decision was left to the discretion of the physician. The primary outcome was a composite of severe adverse neonatal outcome, including brachial plexus injury, intracranial hemorrhage, convulsions, and central nervous system (CNS) depression. Other outcomes of study were scalp/facial lacerations, intracranial hemorrhage, seizures, CNS depression, and admission to the neonatal intensive care unit (NICU). A total of 1730 women were included in the analysis. Of these, 74.7% had no pop-offs, 13.9% had 1 pop-off, 7.4% had 2 pop-offs, and approximately 4% had ≥3 pop-offs. Approximately 94% delivered via VAVD. As the number of pop-offs increased, the number of scalp/facial lacerations, intracranial hemorrhage, subgaleal hemorrhage, convulsions, CNS depression, and NICU admissions significantly increased. However, there was no association with the composite outcome, as well as severe perinatal laceration, shoulder dystocia, brachial plexus injury, and cephalohematoma. Adjusting for confounders, having any number of pop-offs increased the likelihood of scalp/facial lacerations, intracranial hemorrhage, convulsions, CNS depression, and NICU admission. However, there was not a dose-dependent association in the odds of adverse outcomes as the number of pop-offs increased. Compared with having no pop-offs, having any number of pop-offs was associated with an increase in adverse neonatal outcomes. In addition, the rates of intracranial hemorrhage and subgaleal hemorrhage were increased with greater numbers of pop-offs.