OBJECTIVE: To describe the characteristics of pediatric patients prescribed proton pump inhibitors (PPIs) vs those of pediatric patients prescribed histamine-2-receptor antagonists (H2RAs). METHODS: Observational studies were conducted using The Helth Improvement Network (THIN) and the PHARMO Database Network. Patients aged 0-18 years who were first prescribed a PPI or H2RA between October 1, 2009 and September 30, 2012 (THIN) or between September 1, 2008 and August 31, 2011 (PHARMO) were included. Patient characteristics were identified and compared between the PPI and H2RA cohorts using odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex. RESULTS: The mean age (years) was higher in the PPI than in the H2RA cohorts (THIN 12.3 [n = 8204] vs 5.4 [n = 7937], PHARMO 11.0 [n = 15 362] vs 7.1 [n = 6168]). Previous respiratory disease was more common in the PPI than in the H2RA cohort in THIN (OR = 1.19, 95% CI = 1.08-1.30), as were asthma and respiratory medication use in PHARMO (OR = 1.27, 95% CI = 1.12-1.45 and OR = 1.23, 95% CI = 1.10-1.38, respectively) and oral corticosteroid use in both databases (OR = 1.45, 95% CI = 1.10-1.92 [THIN]; OR = 2.80, 95% CI = 2.11-3.71 [PHARMO]). Non-steroidal anti-inflammatory drugs, antibiotics, and oral contraceptives were also more common in PPI than in H2RA cohorts in both databases. CONCLUSIONS: Pediatric patients receiving PPIs and those receiving H2RAs may represent different patient populations. PPIs may be more commonly prescribed than H2RAs among patients with respiratory diseases.