© 2018 American Medical Association. All rights reserved. Importance: It is unclear whether the timing of second stage pushing efforts affects spontaneous vaginal delivery rates and reduces morbidities. Objective: To evaluate whether immediate or delayed pushing results in higher rates of spontaneous vaginal delivery and lower rates of maternal and neonatal morbidities. Design, Setting, and Participants: Pragmatic randomized clinical trial of nulliparous women at or beyond 37 weeks' gestation admitted for spontaneous or induced labor with neuraxial analgesia between May 2014 and December 2017 at 6 US medical centers. The interim analysis suggested futility for the primary outcome and recruitment was terminated with 2414 of 3184 planned participants. Follow-up ended January 4, 2018. Interventions: Randomization occurred when participants reached complete cervical dilation. Immediate group participants (n = 1200) began pushing immediately. Delayed group participants (n = 1204) were instructed to wait 60 minutes. Main Outcomes and Measures: The primary outcome was spontaneous vaginal delivery. Secondary outcomes included total duration of the second stage, duration of active pushing, operative vaginal delivery, cesarean delivery, postpartum hemorrhage, chorioamnionitis, endometritis, perineal lacerations (≥second degree), and a composite outcome of neonatal morbidity that included neonatal death and 9 other adverse outcomes. Results: Among 2414 women randomized (mean age, 26.5 years), 2404 (99.6%) completed the trial. The rate of spontaneous vaginal delivery was 85.9% in the immediate group vs 86.5% in the delayed group, and was not significantly different (absolute difference, -0.6% [95% CI, -3.4% to 2.1%]; relative risk, 0.99 [95% CI, 0.96 to 1.03]). There was no significant difference in 5 of the 9 prespecified secondary outcomes reported, including the composite outcome of neonatal morbidity (7.3% for the immediate group vs 8.9% for the delayed group; between-group difference, -1.6% [95% CI, -3.8% to 0.5%]) and perineal lacerations (45.9% vs 46.4%, respectively; between-group difference, -0.4% [95% CI, -4.4% to 3.6%]). The immediate group had significantly shorter mean duration of the second stage compared with the delayed group (102.4 vs 134.2 minutes, respectively; mean difference, -31.8 minutes [95% CI, -36.7 to -26.9], P <.001), despite a significantly longer mean duration of active pushing (83.7 vs 74.5 minutes; mean difference, 9.2 minutes [95% CI, 5.8 to 12.6], P <.001), lower rates of chorioamnionitis (6.7% vs 9.1%; between-group difference, -2.5% [95% CI, -4.6% to -0.3%], P =.005), and fewer postpartum hemorrhages (2.3% vs 4.0%; between-group difference, -1.7% [95% CI, -3.1% to -0.4%], P =.03). Conclusions and Relevance: Among nulliparous women receiving neuraxial anesthesia, the timing of second stage pushing efforts did not affect the rate of spontaneous vaginal delivery. These findings may help inform decisions about the preferred timing of second stage pushing efforts, when considered with other maternal and neonatal outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02137200.