In order to assess the efficiency of wastewater treatment plants in removing pharmaceuticals from wastewater, sensitive and reliable methods are necessary for trace analysis of these micropollutants in the presence of a highly complex matrix. In this study, conventional activated sludge (CAS) and membrane bioreactor (MBR) treatment systems are compared in eliminating pharmaceuticals in wastewater. The pharmaceuticals investigated include aceclofenac, carbamazepine, diclofenac, enalapril, and trimethoprim. Analysis is performed using a liquid chromatograph with hybrid linear ion-trap mass spectrometer equipped with a polar reversed-phase column to achieve good separation and minimize matrix effects. To pre-concentrate the samples, the use of two types of solid-phase extraction packing materials in tandem assures good recoveries of all the target analytes. In the influent, the concentration of these compounds ranges from 0.09 to 1.4 microg/L. Diclofenac shows resistance to degradation in the CAS but is amenable to degradation in the MBR. Trimethoprim and enalapril are only slightly eliminated in the CAS but are reduced by more than 95% in the MBR. Carbamazepine removal is negligible, while aceclofenac is only 50% reduced in CAS and MBR. In general, these results indicate that MBR has a higher efficiency in removing some polar pharmaceuticals in wastewater.