Abstract Objective Examine the predictive value for maternal-fetal infection of routine bedside tests detecting the proinflammatory cytokines, TNFα and IL-6, in the vaginal secretions of women with premature rupture of the membranes (PROM). Study Design This prospective two-center cohort study included all women hospitalized for PROM over a 2-year period. A bedside test assessed IL-6 and TNFα in vaginal secretions. Both centers routinely tested CRP and leukocytes, assaying both in maternal serum, and analyzed vaginal bacterial flora; all samples were repeated twice weekly until delivery. Results The study included 689 women. In cases of preterm PROM (PPROM) before 37 weeks (n = 184), a vaginal sample positive for one or more bacteria was the only marker associated with early neonatal infection (OR 5.6, 95%CI; 2.0-15.7). Its sensitivity was 82% (95%CI; 62-94) and its specificity 56% (95%CI; 47-65). All positive markers of infection were associated with the occurrence of chorioamnionitis. In cases of PROM from 37 weeks onward (n = 505), only CRP > 5 mg/dL was associated with early neonatal infection (OR = 8.3, 95%CI; 1.1-65.4) or clinical chorioamnionitis (OR = 6.8, 95%CI; 1.5-30.0). The sensitivity of CRP > 5 mg/dL was 91% (95%CI; 59-100) and its specificity 45% (95%CI; 40-51) for predicting early neonatal infection, and 89% (95%CI; 65-99) and 46% (95%CI; 41-51), respectively, for predicting clinical chorioamnionitis. Conclusion The association of vaginal cytokines with maternal-fetal infection is weak and thus prevents their use as a good predictor of maternal-fetal infection. CRP and vaginal samples may be useful for identifying a group of women at low risk of infection.