Abstract Background The lipid content of the chylomicrons is a key biomarker and risk factor of cardiovascular diseases and for the understanding of obesity. A high throughput determination of chylomicrons in human blood plasma is outlined. Methods The new method, which uses a combination of Nuclear Magnetic Resonance (NMR) analysis and multivariate calibration analysis (chemometrics), is based on a correlation analysis towards the established standard method (ultracentrifugation and colorimetric test kit) and enables extraordinarily fast, inexpensive, and robust prediction of triglyceride (TG) content in chylomicrons. It is the position and shape of the complex lipid methylene resonance band that determines the chylomicron TG status and this information is extracted by the multivariate regression method. Results The resulting method is a relatively simple multivariate model that facilitates parsimonious and accurate prediction of chylomicron lipids from NMR spectra of blood. The chemometric model predicts the chylomicron TG content with a correlation coefficient (R) of 0.96 when plotted against density gradient ultracentrifugation data. Conclusions The new rapid method facilitates large scale clinical and nutritional trials with inclusion of diagnostics of chylomicron status and thus creates new opportunities for research in lifestyle diseases and obesity.