This study was designed to evaluate neonatal morbidity and mortality following preterm delivery in the setting of mature amniotic fluid pulmonary studies. We performed a retrospective analysis of all pregnancies resulting in preterm deliveries (< 37 weeks) from 1/1/88 to 5/31/92 in which there was a “mature” phospholipid profile, defined as positive phosphatidylglycerol (PG) or lecithin/sphyngomyelin (L/S) ratio ≥ 2 determined within 1 week of delivery. Excluded were multiple gestations, diabetic pregnancies, and fetal or neonatal abnormalities involving the cardiovascular, renal, or pulmonary tract. Main outcome measures were incidence of significant neonatal morbidity, including respiratory distress requiring respiratory support, sepsis, patent ductus arteriosus, grade 3-4 intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, meningitis, and pneumonia. A total of 1 53 patients fulfilled the inclusion criteria. Mean (SD) gestational age at delivery and birth weight were 33.8 (2.1) weeks and 2298 (561) g, respectively. There were no neonatal deaths, but significant morbidity was present in 20% (31/153) of cases. The most common major neonatal complications were respiratory distress (12%) and suspected or documented sepsis (16%). Univariate analysis showed that frequency of major neonatal morbidity was related to gestational age at delivery (p < 0.001), birth weight (p < 0.001), Apgar score at 5 minutes < 7 (p = 0.008) and method of lung maturity assessment (complications were ore frequent when lung maturity was defined by L/S ≥ 2 than by PG positivity) (p = 0.02). Multivariate analysis demonstrated a significant association between the presence of a neonatal complication and method of lung maturity assessment after adjustment for gestational age at delivery (p = 0.04). The incidence of major neonatal complications among preterm infants is high even in the presence of mature fetal lung studies; this incidence is related primarily to the gestational age at birth, and secondarily to the method of lung maturity testing (complications are less common in the presence of PG positivity than of L/S ≥ 2).