Introduction: Amniotic fluid (AF) interleukin-6 (IL-6) concentration has been associated to preterm delivery and perinatal morbidity and mortality in women with preterm labor and intact membranes. Nevertheless, the clinical significance of this biomarker of intra-amniotic inflammation (IAI) is still unclear due in part to the paucity of large studies. Methods: AF IL-6 concentrations were determined in 452 consecutive women with preterm labor and intact membranes, categorized into 3 groups: 302 without IAI (IL-6 of <2.6 ng/mL), 64 with mild IAI (IL-6 of 2.6–11.2 ng/mL), and 86 with severe IAI (IL-6 of ≥11.3 ng/mL). Results: The severe IAI group had a short pregnancy duration from amniocentesis to delivery (median 3 days) than in without IAI group (median 45 days); meanwhile, the mild IAI group had a latency that was intermediate to the severe and without IAI groups (median 9.5 days). As compared to women without IAI, women with mild and severe IAI had higher rates of preterm delivery at both <34 and <37 weeks of gestation and perinatal morbidity and mortality. Furthermore, the risk of various individual adverse outcomes (short latency from amniocentesis to delivery [at ≤3 days, ≤7 days, and ≤14 days], preterm delivery at both <34 and <37 weeks of gestation, histologic chorioamnionitis, respiratory distress syndrome, and congenital sepsis) was higher in women with severe IAI (OR ≥ 2.8), compared with women without IAI. Conclusions: AF IL-6 concentrations appear to be suitable marker to assess the degree of IAI and are associated with increased risk of adverse outcomes.