High postprandial triglyceridemia shifts HDL size distribution towards large particles. Triglycerides of large HDL increased at 4 h and remained elevated up to 8 h after meal intake in MS patients. HDL3 subclasses became cholesterol-poor during postprandial state in subjects with high incremental area under the curve (iAUC) of TAG. Postprandial hypertriglyceridemia contributes to structural changes of HDL and hypoalphalipoproteinemia.