This study was designed to investigate the efficacy and safety of sulindac in the treatment of preterm labor. Thirty-six women in preterm labor who had failed initial attempts at tocolysis with magnesium sulfate were randomized to receive either oral indomethacin or oral sulindac for 48 hours. The mean gestational ages at admission were 29 and 30 weeks for the sulindac and indomethacin groups, respectively. There was a significantly greater hourly fetal urine output, deepest amniotic fluid pocket, and amniotic fluid index in the sulindac group. A trend toward higher fetal ductus arteriosus flow velocities noted in the indomethacin group was not seen in the sulindac group. The drugs had similar success in delaying delivery for 48 hours or 7 days. The mean birth weights were 2000 and 2323 g for the sulindac and indomethacin groups, respectively. Sulindac appears to be as effective as indomethacin for refractory preterm labor but with fewer fetal side effects.