The risks for preterm birth are heterogeneous and there remains much to elucidate regarding etiology of this adverse perinatal outcome. Antenatal infection with Chlamydia trachomatis, a highly prevalent sexually-transmitted infection, may convey a higher risk of preterm birth. Early detection and eradication of this sexually-transmitted infection without recurrent/persistent infection during pregnancy may serve as an intervention that reduces the risk of preterm birth. The objective of this study was to characterize the association between early antenatal detection and eradication of maternal C. trachomatis infection and the likelihood of preterm birth among pregnant women in an urban county. A retrospective cohort study was conducted in Hamilton County, Ohio (2006-2011) to evaluate the risk of preterm birth among women with maternal C. trachomatis infections detected and eradicated at or before 20 weeks gestation--the intervention group. Infected women whose infections were detected after 20 weeks gestation or persistent during the pregnancy represented the reference group. The study population contained 3,354 pregnant women with documented C. trachomatis infections. The relative risk for moderate to late spontaneous preterm birth (32-36 weeks gestation) was 0.54 (95 % CI 0.37-0.80) for women in the intervention group who were 19 years of age and younger. Pregnant adolescents benefited the most from early detection and eradication of antenatal C. trachomatis infections through a reduction in the risk of PTB at 32-36 weeks gestation. This finding suggests the importance of early antenatal detection and effective treatment of C. trachomatis.