Guan Xin II decoction (GX II) is a widely used traditional Chinese medicine (TCM) formula for the treatment of coronary heart diseases. However, the comprehensive chemical analysis of the formulated GX II is not clarified yet. An HPLC-DAD-ESI-MSn method was established to analyze GX II and its five component herbs, respectively. A total of 57 compounds, including phenolic acids, glycosides, flavonoids, and alkaloids were identified or tentatively characterized on the basis of their mass spectra or by comparison with reference standards. This is the first time that the chemical composition of GX II was elucidated by LC/MS. The established method will be used for quality control and pharmacokinetic studies of GX II.