OBJECTIVE: To assess whether daily gentamicin is as effective as 8-hour gentamicin for the treatment of intrapartum chorioamnionitis. METHODS: Women with a clinical diagnosis of chorioamnionitis between 32 and 42 weeks of gestation were randomly assigned in labor to receive either daily gentamicin (5 mg/kg intravenously (IV), then 2 placebo doses IV after 8 and 16 hours) or 8-hour gentamicin (2 mg/kg IV, then 1.5 mg/kg IV after 8 and 16 hours). Both groups received ampicillin (2 grams IV every 6 hours for a total of four doses). Patients who underwent cesarean delivery also received clindamycin (900 mg IV every 8 hours, for a total of three doses). The primary outcome was treatment success, defined by resolution of chorioamnionitis after 16 hours of treatment without development of endometritis. One hundred twenty-six patients were required to have 95% confidence that daily gentamicin is at worst 15% inferior to 8-hour dosing with an alpha of .05 and a beta of 0.2. Results: One hundred twenty-six women were enrolled, of whom 63 received daily gentamicin and 63 received 8-hour gentamicin. One patient was excluded from data analysis. Baseline maternal and obstetric characteristics were similar between groups except for longer mean duration of ruptured membranes in the 8-hour group (679±514 compared with 469±319 minutes; P =.03). Treatment success was equal between groups (94% daily gentamicin compared with 89% 8-hour gentamicin, P =.53). There were no differences in maternal or neonatal morbidities, including neonatal sepsis and newborn hearing screen. Conclusion: Daily and 8-hour gentamicin appear equally effective for the treatment of intrapartum chorioamnionitis. Clinical trial registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00185991.