Detection of sulfur-fumigated Paeoniae Alba Radix (PAR) in different complex preparations is challenging due to the relatively lower content of PAR and interference from more complicated components in complex preparations with different multiple constituent herbs. In this study, a high performance liquid chromatography- triple-quadrupole tandem mass spectrometry method was developed for detecting sulfur-fumigated PAR in different complex preparations. Paeoniflorin, the major component of PAR, and paeoniflorin sulfonate, the characteristic artifact transformed from paeoniflorin during sulfur-fumigation of PAR, were used as chemical markers. Multiple reaction monitoring (MRM) scan was employed to maximize sensitivity and selectivity. Through optimizing full mass scan and daughter ion scan conditions, two mass transitions were selected and employed respectively for unequivocal identification of paeoniflorin and paeoniflorin sulfonate. The detection limits for paeoniflorin and paeoniflorin sulfonate using MRM were much lower than those detected with UV 270 nm. Paeoniflorin and paeoniflorin sulfonate could be simultaneously detected in different commercial PAR-containing complex preparations without interference of other components using the established method, indicating that the newly established method was selective and sensitive enough for screening sulfur-fumigated PAR in commercial complex preparations.