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Yeonkyopaedok-san is a traditional Korean medicine used in the early treatment of boils. In the present study, its 12 marker components for quality control were determined using high-performance liquid chromatography (HPLC) with photodiode array detection and ultra-performance liquid chromatography&#8722;mass spectrometry with tandem mass spectrometry (UPLC&#8722;MS/MS). The investigated 12 marker components of Yeonkyopaedok-san were as follows: 3-caffeoylquinic acid, cimifugin 7-glucoside, liquiritin apioside, ferulic acid, narirutin, 5-<i>O</i>-methylvisammioside, naringin, neohesperidin, oxypeucedanin hydrate, arctigenin, glycyrrhizic acid, and 6-gingerol. The analytical column used for the separation of the 12 marker analytes in Yeonkyopaedok-san was a Waters SunFire C18 column (4.6 mm &#215; 250 mm, 5 &#956;m). The two mobile phases used were 0.1% (<i>v</i>/<i>v</i>) aqueous formic acid and 0.1% (<i>v</i>/<i>v</i>) formic acid in acetonitrile. In the UPLC&#8722;MS/MS analysis, all components were separated using a Waters ACQUITY UPLC BEH C18 column (2.1 mm &#215; 100 mm, 1.7 &#956;m). The two mobile phases used were 0.1% (<i>v</i>/<i>v</i>) aqueous formic acid and acetonitrile. The coefficient of determination of the calibration curves in both analysis systems showed good linearity (&gt;0.99). The amounts of the 12 marker components in Yeonkyopaedok-san determined using HPLC&#8722;photodiode array detection and UPLC&#8722;MS/MS analyses were found to be 0.14&#8722;9.00 mg/g and 2.35&#8722;853.11 &#956;g/g, respectively.