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Practice patterns regarding pediatric gastroesophageal reflux disease include acid suppression for infants meeting certain clinical criteria. This study aimed to examine the use of proton pump inhibitors (PPI) in infants and neonates.This retrospective observational study used data from 1999 to 2004 from 4 health care plans in the United States. Infants age <12 months with at least 1 pharmacy claim for a PPI were identified. Demographic information and PPI utilization patterns were assessed. Medical charts were reviewed in a subset of patients to gather dosing information.Identified infants (N = 2469) were 58% male. PPI use rose 4-fold from 2000 to 2003; lansoprazole and omeprazole were almost exclusively used. Treatment for almost half of the patients was initiated by their fourth month of life. The most common diagnoses identified through medical claims included gastroesophageal reflux (59%), problems feeding (23%), upper respiratory infections (23%), esophagitis (21%), and pain from gas (20%). Preindex H2 blockade was evident in 58% of the patients; preindex metoclopramide was used in 38% of the patients. Longer duration of PPI therapy was associated with patients who had more comorbidities. Through chart review of 388 patients, a subset of 272 patients with dosing information revealed that a median daily dosage in patients receiving lansoprazole was 1.74 mg · kg−1 · day−1 compared with 1.21 mg · kg−1 · day−1 for omeprazole.PPI use in the study population increased steadily from 1999 to 2004. These data offer valuable information on current PPI dosing patterns that may be used to design future clinical trials for assessment of gastroesophageal reflux disease regimens and clinical outcomes in the infant population.