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Over 20% of culture-positive untreated pregnant women develop pyelonephritis and other symptomatic disease. The risk of pyelonephritis in pregnant women with asymptomatic bacteriuria is reduced by treatment with antibiotics. It is unclear whether 1-day antibiotic therapy or treatment for several days has similar efficacy. Nitrofurantoin is one of several antibiotics used for treatment in such women. This multicenter, double-blind, placebo-controlled, randomized controlled trial compared the effectiveness of 1-day treatment and 7-day treatment with nitrofurantoin in eradicating asymptomatic bacteriuria in pregnant women. The study subjects were seen between 2004 and 2007 at antenatal clinics in Thailand, the Philippines, Vietnam, and Argentina that were part of the World Health Organization Maternal and Perinatal Research Network. Pregnant women were randomized to receive nitrofurantoin 100 mg twice daily either for 1 day (1-day group, n = 386) or 7 days (7-day group, n = 392). Bacteriologic cure was the primary study outcome.Cultures were positive for 1248 of 24,430 eligible women, for an overall asymptomatic bacteriuria prevalence of 5.1%. The most common causative pathogens identified at enrollment in both treatment groups were similar; Escherichia coli was the most common and was found in nearly 50% of the women. Following 14 days of treatment, bacteriologic cure rates were significantly greater among women in the 7-day group than those in the 1-day group (86.2% vs. 75.7%), with a cure rate difference of −10.5% (95% confidence interval [CI], −16.1% to −4.9%). The infants of women in the 1-day group had a significantly lower mean birth weight (1 day: 3,059 gm vs. 7 days: 3159 gm, with a mean difference of −100 [95% CI, −181 to −18]), and lower mean gestational age (1 day: 38.4 weeks vs. 7 days: 38.7 weeks, with a mean difference of −0.3 [95% CI, −0.7 to −.005]). There no statistically significant differences in adverse effects between the treatment groups.These data demonstrate that 7 days of treatment with nitrofurantoin is significantly more effective than 1 day of treatment in achieving bacteriologic cure in pregnant women with asymptomatic bacteriuria and is preferred.