A rapid, sensitive, reproducible, and accurate ultraperformance liquid chromatographic (UPLC) method was developed for the simultaneous determination of 10 diterpenoid compounds (tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I, 1,2-dihydrotanshinquinone, methylenetanshinquinone, miltirone, 5,6-dehydrosugiol, sugiol, and przewalskin) in Salvia miltiorrhiza for the first time. Central composite design was applied as a powerful tool to optimize the most dominant parameters that influence the resolution of UPLC, that is, gradient, flow rate, and column temperature. Under optimum conditions, all peaks except 1,2-dihydrotanshinquinone and methylenetanshinquinone could be baseline separated within 8 min. Furthermore, the contents of these compounds in S. miltiorrhiza samples collected from different provinces of China have also been compared. The results showed that UPLC is one of the most efficient methods for the analysis of diterpenoid compounds in S. miltiorrhiza and that it is a potential method for quality control of this valuable traditional Chinese medicine. © 2008 American Chemical Society.