Study objectives: The prevalence of gastroesophageal reflux disease (GERD) is higher in people with asthma than in control populations. Predisposing factors for GERD development may include asthma medications such as prednisone. The objective of this study was to determine whether prednisone alters GERD parameters in people with asthma. Design: Prospective, single-blinded, placebo-controlled, crossover study. Setting: University medical center clinic. Participants: Twenty adults with stable, moderate persistent asthma with minimal esophageal reflux symptoms (less than three times a week) who were not receiving antireflux therapy. Intervention: Prednisone, 60 mg/d, for 7 days. Measurements and results: Asthma, esophageal reflux symptoms, and spirometry were measured during baseline, placebo, and prednisone phases, each 7 days in duration. Dual-probe esophageal pH monitoring, esophageal and respiratory manometrics (20 subjects), and basal and stimulated gastric acid secretion (4 subjects) were measured after placebo and prednisone phases. There were significant increases in esophageal acid contact times at the distal and proximal pH probes during the prednisone phase. Total percentage of time that pH was < 4.0 at the distal probe was 2.5 ± 0.4% for placebo compared with 5.9 ± 0.9% for prednisone (p < 0.002). Total percentage of time that pH was < 4.0 at the proximal probe was 0.3 ± 0.1% for placebo and 0.8 ± 0.2% for prednisone (p < 0.0007). There were no significant changes in subject weight, spirometry, asthma or esophageal reflux symptoms, manometrics, or basal or stimulated gastric acid secretion. Conclusion: Prednisone, 60 mg/d for 7 days, increased esophageal acid contact times in this small population of people with stable asthma; however, the mechanism for this finding is unclear.