Background. Previous studies have suggested that chronic periodontal infection may be associated with preterm births. The authors conducted a prospective study to test for this association. Methods. A total of 1,313 pregnant women were recruited from the Perinatal Emphasis Research Center at the University of Alabama at Birmingham. Complete periodontal, medical and behavioral assessments were made between 21 and 24 weeks gestation. After delivery, medical records were consulted to determine each infant's gestational age at birth. From these data, the authors calculated relationships between periodontal disease and preterm birth, while adjusting for smoking, parity (the state or fact of having born offspring), race and maternal age. Results were expressed as odds ratios and 95 percent confidence intervals, or CIs. Results. Patients with severe or generalized periodontal disease had adjusted odds ratios (95 percent CI) of 4.45 (2.16-9.18) for preterm delivery (that is, before 37 weeks gestational age). The adjusted odds ratio increased with increasing prematurity to 5.28 (2.05-13.60) before 35 weeks' gestational age and to 7.07 (1.70-27.4) before 32 weeks' gestational age. Conclusions. The authors' data show an association between the presence of periodontitis at 21 to 24 weeks' gestation and subsequent preterm birth. Further studies are needed to determine whether periodontitis is the cause. Clinical Implications. While this large prospective study has shown a significant association between preterm birth and periodontitis at 21 to 24 weeks' gestation, neither it nor other studies to date were designed to determine whether treatment of periodontitis will reduce the risk of preterm birth. Pending an answer to this important question, it remains appropriate to advise expectant mothers about the importance of good oral health.