A quality assurance (QA) procedure for multiple-herb extraction, which takes into account the existence of common chemical markers and multiple-herb-extraction effects, has been developed for producing Chinese herbal medicines (CHMs) of consistent quality. The experimental method for determining related correlation function of the multiple-herb-extraction effect was designed. A systematic solution strategy was also developed to appropriately decompose the multiple-herb extraction system into several subsystems for obtaining solution(s) and determining the overall behavior of the system. An example of QA of Danshen-Gegen (DG) decoction was used to demonstrate the QA procedure. An H9c2 cell assay was used to test the efficacy of consistent quality DG decoctions prepared by different herb combinations with different material costs of herbs. It was observed that a multiple-herb-extraction effect was present in the aqueous extraction of Danshensu and this effect was depended on the extraction solvent. The possible mechanism of this multiple-herb-extraction effect in the aqueous DG extraction was speculated to be the change of initial pH value of the aqueous extraction solvent by an unknown component from Gegen. The experimental chemical marker concentrations fell within +/- 10% of the specified chemical marker compositions by using the amount of herb from each herb class as predicted by the QA model. Furthermore, an H9c2 cell assay was used to test the efficacy of three consistent quality DG extracts, which were produced by different herb combinations with different material costs of herbs. The results showed that the three DG extracts provided consistent biological efficacy against menadione-induced toxicity. This study extended a recently developed QA procedure of single-herb extraction to multiple-herb extraction. It provides a solution of QA in extraction, which is one of the most important unresolved problems in the modernization of traditional Chinese medicines. With this modified model and the companion experiments, the amount of herbs needed from different quality classes to produce a multiple-herb formula CHM product decoction with consistent quality can be exactly determined. (c) 2014 American Institute of Chemical Engineers AIChE J 60: 4014-4026, 2014