Objectives: To determine whether concentrations of β-HCG in cervicovaginal secretions could predict spontaneous preterm birth (SPB) in asymptomatic high risk pregnancies. Methods: A cohort study was undertaken with cervicovaginal samples collected from 540 pregnant women between 20 to 28 weeks of gestation. Levels of β-HCG were measured by ELISA test. Results: There was 3.2-fold increase in cervicovaginal β-HCG concentrations among patients with SPB vs. term delivery. A single cervicovaginal β-HCG >77.8mIU/ml, between 20 and 28 weeks' gestation, identified patients with subsequent SPB vs. term delivery with sensitivity of 87.5% (95% CI: 47.4-97.9) and a specificity of 97% (95% CI: 86.5-99.4) with positive and negative predictive values of 88.5% and 98%, respectively. Multiple logistic regression indicates that cervicovaginal β-HCG level >77.8mIU/ml was an independent predictor of SPB (adjusted odds ratio 19.97, 95% CI: 10.65-37.45). Conclusions: Cervicovaginal β-HCG is a sensitive and specific predictor of patients with subsequent preterm delivery.