To test the hypothesis that genital colonization with Ureaplasma urealyticum would predict adverse pregnancy outcome, 4934 women from five medical centers were evaluated for vaginal colonization with U. urealyticum between 23 and 26 weeks' gestation and followed up to delivery. U. urealyticum colonization was associated with maternal age, parity, racial-ethnic group, martial status, income, education, smoking, number of sexual partners, and colonization with Trichomonas vaginalis, Mycoplasma hominis, and bacterial vaginosis. After adjustment for medical and sociodemographic factors in a multivariate analysis, there was no difference in the mean birth weight or proportion of low-birth-weight infants delivered by women who carried U. urealyticum and those who did not. U. urealyticum colonization at 23 to 26 weeks was not associated with preterm rupture of membranes, preterm labor, or preterm delivery. A positive vaginal culture for U. urealyticum in midgestation does not predict those women at risk for preterm labor, preterm delivery, preterm premature rupture of membranes, or delivery of a low-birth-weight infant.