Objective: To compare outpatient to inpatient management of acute pyelonephritis in pregnancy beyond 24 weeks’ gestation. Methods: Ninety-two gravidas past 24 weeks’ gestation, randomized to outpatient or inpatient therapy, received two 1-g doses of intramuscular ceftriaxone at 24-hour intervals while hospitalized, then were discharged and reevaluated within 48–72 hours or remained hospitalized until afebrile for 48 hours. Subjects received oral cephalexin after initial treatment. Urine cultures were done on admission and 5–14 days after therapy. Surveillance continued until delivery. We anticipated that 15% of outpatients and 0.01% of inpatients would require changes in antibiotic therapy. Results: Twenty-one percent of women evaluated were excluded. Thirteen of 46 (28%) outpatients’ hospitalization exceeded 24 hours. Six outpatients (13.0%) and one inpatient did not respond to initial therapy and were treatment failures (relative risk [RR] 1.82, 95% confidence interval [CI] 1.00, 3.31). Within 2 weeks of initial therapy, seven of 81 (8.6%) subjects had positive urine cultures, four outpatients versus three inpatients (P > .999). Eleven of 84 (13.1%) deliveries for which birth data were available occurred preterm (six of 41 outpatients versus five of 43 inpatients) (RR 1.14, 95% CI 0.61, 2.11). Conclusion: There were no significant differences in clinical responses or birth outcomes of inpatients or outpatients treated for acute pyelonephritis after 24 weeks’ gestation if they completed their assigned protocols. Thirty percent of outpatients were unable to, and most women with acute pyelonephritis in the third trimester were not candidates for outpatient therapy.