XiaoShuanTongLuo (XSTL) is an important multi-herbal formula widely used as a traditional Chinese medicine (TCM). In this paper, an ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric method (UPLC-ESI-MS/MS) was developed for the simultaneous identification and quantification of 18 chemical constituents in the extract of XSTL. The analysis was performed in multiple-reaction monitoring (MRM) mode using positive and negative electrospray ionization (ESI). A BEH C18 (2.1 mm× 100 mm, 1.7 μm) column with a gradient mobile phase of methanol-0.1% aqueous formic acid solution at a flow rate of 0.2 mL/min was used for separation. The standard curves of most components showed good linearity over the concentration range of 0.001-0.5 μg/mL with r = 0.9896-0.9996. The relative standard deviations (RSD) of intra-day and inter-day precision were all lower than 15% at low, middle, and high concentration levels. The RSD of stability analysis in 24 h were also lower than 15%. The validated method was employed to quantify 18 active components simultaneously in four different commercial brands of XSTL products in various dosage forms. The developed method was rapid, accurate, sensitive, and reproducible for the quality control of XSTL.