OBJECTIVE: Our aim was to determine whether the presence of fetal fibronectin in vaginal secretions of patients with symptoms suggestive of preterm labor predicts preterm delivery. STUDY DESIGN: Patients who were examined at the hospital between 24 weeks' and 84 weeks 6 days' gestation with intact membranes, no prior tocolysis, symptoms suggestive of preterm labor, and cervical dilation <3 cm were recruited at 10 sites. Swabs of the posterior fornix were assayed for the presence of fetal fibronectin by monoclonal antibody assay, with a positive result defined as ≤50 ng/ml. Results were not available to the managing physicians. Tocolysis was used when clinically indicated after specimen collection. RESULTS: A total of 763 patients had fetal fibronectin results and pregnancy outcome data available for analysis. Fetal fibronectin was detected in specimens from 150 (20%) patients. Compared with patients who had negative results, patients who had positive results for fetal fibronectin were more likely to be delivered within 7 days (relative risk 25.9 [95% confidence interval 7.8 to 86]), within 14 days (relative risk 20.4 [95% confidence interval 8.0 to 53]), and before 37 completed weeks (relative risk 2.9 [95% confidence interval 2.2 to 3.7]). The negative predictive values for delivery within 7 days, within 14 days, and at <37 weeks were 99.5%, 99.2%, and 84.5%, respectively. When we used multiple logistic regression analysis to control for potential confounding variables among singleton pregnancies, only the presence of fetal fibronectin (odds ratio 48.8, 95% confidence interval 7.4 to 320), prior preterm birth (odds ratio 8.3, 95% confidence interval 1.5 to 46.6), and tocolysis (odds ratio 4.1, 95% confidence interval 1.0 to 16.0) were associated with birth within 7 days; fetal fibronectin (odds ratio 3.6, 95% confidence interval 2.2 to 5.9), prior preterm birth (odds ratio 2.5, 95% confidence interval 1.4 to 4.4), cervical dilatation >1 cm (odds ratio 2.9, 95% confidence interval 1.6 to 5.2), and tocolysis (odds ratio 4.5, 95% confidence interval 2.8 to 7.2) were all independently associated with delivery before 37 weeks. CONCLUSION: In a population of patients with symptoms, the presence of fetal fibronectin in vaginal secretions best defines a subgroup at increased risk for delivery within 7 days; the high negative predictive value of fetal fibronectin sampling supports less intervention for patients with this result.