OBJECTIVE: Low serum ferritin levels correlate with low iron stores, whereas high levels are associated with an acute-phase reaction. Our objective was to determine whether elevated levels of ferritin in the genital tract may be a potent marker to identify patients at risk for spontaneous preterm delivery. STUDY DESIGN: We performed a nested case-control study involving 182 women who had spontaneous preterm delivery and 182 term control subjects matched for race, parity, and recruitment center, and selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Development Maternal-Fetal Medicine Units Network. Cervical fluid ferritin was measured by use of radioimmunoassay. RESULTS: Cervical ferritin levels were significantly higher in women who subsequently had spontaneous early preterm delivery (<32 weeks, mean ± SD, 37.7 ± 31.1 vs 21.5 ± 24.1 ng/mL, P = .002; and <35 weeks, 43.2 ± 62.7 vs 28.2 ± 36.7 ng/mL, P = .004) than in term controls. A cervical ferrifin of >75th percentile in the controls (>35.5 ng/mL) was found in 52.9% (9/17) of the women delivered <29 weeks vs 17.7% (3/17) of the controls (odds ratio [OR] 5.3 [95% CI 1.1 -25.2]) and in 43.5% (20/46) of the women delivered <32 weeks versus 10.9% (5/46) of the controls (OR 6.3, 95% CI 2.1-18.9). Cervical ferritin levels had a weaker association with spontaneous preterm delivery <35 weeks (OR 2.8 [95% CI 1.5-5.1]) and <37 weeks (OR 1.6, 95% CI 1.0-2.5]). Cervical ferritin levels correlated significantly with cervical lactoferrin, interleukin-6 (IL-6), and defensin levels. CONCLUSIONS: Elevated cervical ferritin levels at 22 to 24 weeks of gestation in asymptomatic women are associated with subsequent spontaneous preterm birth. The strong correlation of cervical ferritin with other inflammatory markers provides support for the hypothesis of infection as a mediator of preterm delivery.