Background/Aims:  Dyspepsia symptoms of abdominal discomfort, fullness, early satiety, and nausea occur after ingestion of meals in 20–30% of the population. Gastric dysrhythmias are exhibited by approximately 55% of dyspepsia patients. Currently there are limited therapies to reduce these symptoms. Gastric and pancreatic lipases are key enzymes in fat digestion, and hydrolyze fat into fatty acids and monoglycerides. The aims of this study were to characterize the effects of a high fat meal on upper gastrointestinal symptoms and gastric myoelectrical activity, and to evaluate the effect of acid‐resistant lipase supplementation on the same outcomes. Methods:  Sixteen healthy volunteers enrolled in a double‐blind, placebo controlled, cross‐over trial were given a high fat meal (Pulmocare®) that was 55% fat, 28% carbohydrates, and 17% protein (237 ml; 355 Kcal). A capsule containing 280 mg of acid‐resistant lipase (Amano Enzyme USA) or placebo was administered immediately before ingestion of the meal. The order of conditions was counterbalanced, and visits were separated by at least one week. At each visit, individuals completed a Visual Analog Scale (VAS) concerning symptoms of nausea, stomach fullness, hunger, bloating, and abdominal discomfort at baseline, immediately after the meal, and at 10, 20, 30, 45, and 60 minutes after the meal. Electrogastrograms (EGGs) were recorded throughout each visit to assess gastric myoelectrical activity. Results:  Nausea, bloating, and stomach fullness were significantly increased 10 min after ingestion of the meal (ps < 0.05), and hunger was significantly decreased (p < 0.001); there was also a significant decrease in normal gastric myoelectrical activity (3 cycles min−1), and a significant increase in tachygastria (3.7–10 cycles min−1) at 10 min after the meal (ps < 0.05). By 45 min after the meal, dyspepsia symptoms and tachygastria had decreased significantly from immediately after the meal, and normal gastric myoelectrical activity had increased significantly (ps < 0.05). Stomach fullness was significantly lower with lipase supplementation than with placebo condition at 20 and 30 min after the meal (p < 0.05); no effect of lipase supplementation on gastric myoelectrical activity was detected. Conclusions:  (1) The high fat meal induced dyspepsia symptoms and gastric dysrhythmias, suggesting the meal may be a useful test for assessing gastric neuromuscular disorders; and (2) Acid‐resistant lipase supplementation decreased stomach fullness after ingestion of the meal, and warrants further study in individuals with functional dyspepsia.