High fat enteral formulas have been advocated for the nutritional support of chronic obstructive pulmonary disease (COPD) patients because dietary fat utilization under ideal conditions produces less CO2 per O2 consumed than carbohydrate. No data exist for these patients comparing the effects of a moderate fat vs. a high fat enteral formula on gastric emptying times (GE) and subsequent CO2 production (VCO2), oxygen consumption (VO2), respiratory quotient (RQ), and pulmonary function. Our double-blind crossover study compared these parameters after feeding a 355 mL (530 kcal) meal with either 41% fat calories (Respalor) or 55% fat calories (Pulmocare). Thirty-six COPD outpatients with a forced expiratory volume in 1 s (FEV1) < 60% of predicted were studied after an overnight fast. Gastric emptying half-time (GE t1/2) was measured using the 99MTc-radionuclide technique; VCO2, VO2, RQ, and other pulmonary functions were measured at 0, 30, 90, and 150 min postprandial using the Canopy Mode of the Deltatrac Metabolic Monitor and the Renaissance Spirometry System. We observed a significantly (p = 0.0001) longer GE t1/2 of the high fat meal when compared to the moderate fat meal (134.1 vs. 108.6 min) At 30 and 90, but not at 150 min postprandial, the VCO2 and VO2 for patients fed the moderate-fat formula were significantly (p = 0.05) higher than for those fed the high-fat formula; no differences were observed for the other pulmonary functions. Although RQ increased significantly (p = 0.01) after both meals, no differences between formulas were noted at all postprandial times tested. Compared to the high-fat meal, the moderate-fat meal significantly enhanced gastric emptying. The earlier rise in VCO2 and VO2 after the moderate-fat meal did not impact pulmonary function and reflected the earlier utilization of the moderate-fat meal. The fact that RQ was not different between the two meals at all postprandial times tested suggest that the higher rise in VCO2 and VO2 after the moderate-fat meal was most likely due to earlier gastric emptying of the moderate-fat meal rather than the difference of the fat-to-carbohydrate ratio between the two tested meals. The impact of these findings on long-term management of COPD patients awaits long-term prospective studies.