The aim of the study was to implement a mathematical model to simulate two-phase anaerobic digestion (TPAD) process which consisted of an anaerobic continuous stirred tank reactor (CSTR) and an upflow anaerobic sludge blanket (UASB) reactor in series treating traditional Chinese medicine (TCM) wastewater. A model was built on the basis of Anaerobic Digestion Model No. 1 (ADM1) while considering complete mixing model for the CSTR, and axial direction discrete model and mixed series connection model for the UASB. The mathematical model was implemented with the simulation software package MATLABTM/Simulinks. System performance, in terms of COD removal, volatile fatty acids (VFA) accumulation and pH fluctuation, was simulated and compared with the measured values. The Simulation results indicated that the model built Was able to well predict the COD removal rate (-4.8-5.0%) and pH variation (-2.9-1.4%) of the UASB reactor, while failed to simulate the CSTR performance. Comparing to the measured results, the simulated acetic acid concentration of the CSTR effluent was underpredicted with a deviation ratios of 13.8-23.2%, resulting in an underprediction of total VFA and COD concentrations despite good estimation of propionic acid, butyric acid and valeric acid. It is presumed that ethanol present in the raw wastewater was converted into acetic acid during the acidification process, which was not considered by the model. Additionally, due to the underprediction of acetic acid the pH of CSTR effluent was overestimated. (C) 2009 Elsevier Ltd. All rights reserved.