OBJECTIVE We compared the safety of celecoxib, a selective cyclo-oxygenase-2 inhibitor, with the safety of the nonselective cyclo-oxygenase inhibitor indomethacin, when it was administered for treatment of preterm labor. METHODS In a randomized, double-blind, placebo-controlled trial, 24 pregnant women in preterm labor at 24 to 34 weeks of gestation received either indomethacin or celecoxib for 48 hours. Clinical assessment, fetal sonography, and Doppler blood flow studies of the fetal ductus arteriosus were performed daily. RESULTS Mean maximum ductal flow velocity was significantly elevated over baseline (82.9 +/- 4.6 cm/s vs 111.14 +/- 14.3 cm/s; P =.02) after 24 hours of indomethacin, but not celecoxib. Both medications were associated with a transient decrease in amniotic fluid volume, with a greater effect by indomethacin. The medications were equally effective in the maintenance of tocolysis. There were no significant maternal or neonatal adverse events. CONCLUSIONS In this initial evaluation, the safety of short-term celecoxib in women with preterm labor was superior to that of indomethacin.