Objective: To study the association between neonatal CLD and GERD in VLBW infants and to identify risk factors for GERD among infants with CLD. Design: Restrospective cohort study. Methods: CLD was defined as the need for supplemental oxygen at 36 weeks post-conception. The study sample included 375 infants with CLD admitted consecutively to one of two nurseries which are the sole providers of neonatal intensive care in a 17-county region, and 345 controls, without CLD, who were matched with CLD infants in terms of gestational age. All infants were born 1/1/85 to 5/31/95, had birth weight < 1500 gm, survived to discharge, and were followed through one year adjusted age. Records were reviewed to ascertain the following: the use of anti-reflux medications in the hospital and after discharge; the results of the following tests (when performed): pH probe, upper gastrointestinal contrast studies, and microscopic examination of tracheal aspirates for lipid-laden macrophages; and the requirement for fundoplication. Results: Infants with CLD were similar to controls in gestational age [CLD:27 (24-31); controls: 28 (24-31)], but had lower birth weight [CLD: 900 (584-1402); controls: 1040 (658-1400) gms; p < 0.001] and were more likely to be males [57% vs 43%; p<0.001]. CLD was associated with the use of anti-reflux medications in the hospital [CLD: 25%, controls: 10%; odds ratio: 3.2 (2.1-4.9); p <0.0001] and at discharge [CLD: 27%, controls: 9%; odds ratio: 4.2 (2.7-6.5); p <0.0001]. Infants with CLD were tested more often for reflux [CLD: 14%; controls: 4%; odds ratio: 5.2 (2.7-10.2); p< 0.0001], but a significant association was not found between CLD and a positive test for reflux [CLD: 80%; controls: 64%; odds ratio: 2.3 (0.6-9.2); p = 0.2]. Fundoplication was required in 2% and 0% of infants with CLD and control infants respectively [odds ratio: 5.6 (0.7-46.7); p=0.07]. Among infants with CLD, no association was found between GERD and any of the following: gestational age, hyperinflation on chest radiography, duration of oxygen requirement, or severity of intracranial hemorrhage.Conclusions: This analysis suggests that among VLBW infants, those with CLD are more often treated for GERD. Among infants with CLD, treatment for GERD was not associated with degree of prematurity, hyperinflation on chest radiography, or duration of supplemental oxygen use.