We conducted a double-blind, controlled study to investigate the effects of prolonged ingestion of margarine containing medium-chain triglycerides (MCT-M) on serum lipids, apolipoprotein and vitamin A levels, and on postprandial thermogenesis, compared with those of margarine containing long-chain triglycerides (LCT-M). Healthy subjects (n = 26, Body Mass Index 22.6 ± 3.3 kg/m², mean ± SD) were divided into two groups and ingested 1950-2400 kcal/day of energy, 59-69 g/day of total fat, and 42 g/day of test margarine (15 g/day of MCT or LCT) for 4 weeks. Intake of medium-chain fatty acids was significantly greater with the MCT-M diet (14.2 ± 0.4 g/day, mean ± SD) than with the LCT-M diet (0.2 ± 0.0 g/day) during the 4-week period. There were no significant differences in the blood concentrations of lipids, lipoproteins, apolipoproteins, retinol, glucose, insulin, ketone, hemocytes and electrolytes, or in measures of liver and renal function, between the diet groups. After prolonged ingestion of MCT-M, consumption of an MCT-M meal led to a significant increase in postprandial O₂ consumption compared with an LCT-M meal (after 30 min: MCT-M 45 ± 7 ml/min vs. LCT-M 30 ± 7 ml/min; mean ± SE). In conclusion, we suggest that the influences of ingestion of MCT-M for 4 weeks on serum lipids, lipoproteins, apolipoproteins, retinol, ketones, plasma glucose and liver and renal function were similar to those of LCT-M. We also suggest that the prolonged ingestion of 15 g of MCT in healthy humans did not attenuate the postprandial thermogenesis caused by meals containing 5 g of MCT. From these suggestions, MCT-M have a possibility of being efficient foodstuff for preventing obesity in healthy humans.