BACKGROUND & AIMS: The effects of diet on gastroesophageal reflux disease are not well understood. This study assessed the effects of dietary fat and calorie density on esophageal acid exposure and reflux symptoms in patients with reflux symptoms. METHODS: Patients referred for the investigation of reflux symptoms were recruited (most with nonerosive disease). A catheter-free system provided esophageal pH monitoring over 4 days in 4 dietary conditions. A high-fat (50%) vs low-fat (25%) diet (calorie-controlled), and a high-calorie (1000 kcal) vs low-calorie (500 kcal) diet (fat-controlled) were provided in randomized order, and meal volume was controlled. The effects of meal consistency also were studied. RESULTS: Complete data were available for 15 patients (6 men, 9 women; age, 48 y; range, 26-70 y; body mass index, 26 kg/m2; body mass index range, 21-35 kg/m2). Demographic variables and meal sequence had no effect on reflux parameters. Dietary composition had effects on esophageal acid exposure (F statistic [analysis of variance] = 7.4, P < .005) and symptoms (Friedman test = 24.2, P < .001). No effect of meal consistency was present. Esophageal acid exposure was greater during the high-calorie than the low-calorie diet (mean, 8.6% +/- 2.0% vs 5.2% +/- 1.4% time pH < 4/24 h; P < .01). No difference was observed between the high-fat and low-fat diets (mean, 8.6% +/- 2.0% vs 8.2% +/- 1.6% time pH < 4/24 h; P = NS). In contrast, the frequency of reflux symptoms was not affected by calorie density (median, 6; range, 2-12 vs median, 8; range, 2-13; P = NS) but was increased by the high-fat compared with the low-fat diet (median, 11; range, 5-18 vs median, 6; range, 2-12; P < .05). CONCLUSIONS: Calorie density determines the severity of esophageal acid exposure in gastroesophageal reflux disease after a meal; however, the percentage fat content of the diet has important effects on the frequency of reflux symptoms.