Acetaminophen (APAP) is widely used for pain management during pregnancy with a mechanism known to selectively suppresses peripheral prostaglandin E2 (PGE2) release. Dinoprostone is a naturally occurring PGE2 used for induction of labor. This study sought to determine if acetaminophen's suppressive activity on peripheral PGE2 effects the efficacy of dinoprostone for induction of labor. We conducted a 5 year retrospective cohort study and reviewed charts on women who received dinoprostone for induction of labor at term. Term pregnancies were defined as pregnancies between 40-42 weeks gestational age without onset of labor and a bishop score of 6 or less. Patients were included in the study if there received dinoprostone vaginally in doses of 10mg every 12 hours as needed for induction for a late term pregnancy and received between 2000-4000mg of APAP per day over the course of their induction. Patients receiving magnesium sulfate in the context of preeclampsia with severe features excluded. The study included 631 patients, with 303 receiving at least 2000mg of acetaminophen and 328 who did not. Baseline characteristics were not significantly different between treatment groups. Patients receiving acetaminophen experienced a longer duration of induction of labor 9.2±0.9 (1.6-13.7) hours as compared with those not receiving acetaminophen 6.3±1.1 (0.8-10.3), p = 0.02. In crude analysis, compared to those not receiving acetaminophen, receiving acetaminophen was associated with a 32% increased risk of requiring a second dose of dinoprostone (RR 1.78, 95% CI 1.42-1.93, p = 0.04.) After adjusting for BMI, initial cervical dilation at presentation, bishop score, diabetes mellitus, gestational blood pressure >140/90, race, advanced maternal age ( >34 y), and parity, this risk remained significant. APAP use ranging between 2000-4000mg over the course of a patient's labor induction with vaginal dinoprostone appears to be associated with a longer duration of induction. In such cases, other methods of cervical ripening may be a more suitable choice.