The abuse of paramethoxymethamphetamine (PMMA) and 3,4-methylenedioxymethamphetamine (MDMA) among young people is increasingly serious and has become a public health problem. Since enantiomers of MDMA and PMMA are metabolized at different rates in the body and exhibit different neurotoxicity in tissues, we have developed a simple method for simultaneous enantiomeric determination of PMMA and MDMA, using parallel dual capillary immunoaffinity columns coupled with tandem mass spectrometry. Linear calibration curves were obtained in concentration ranges of 100–1000 ng/mL, with a limit of quantitation of <22 ng/mL. Good interday accuracy and precision were achieved with this method. Besides filtering the urine sample through a 0.45 μm MILLIPORE membrane, no other sample pretreatment was needed, and no toxic organic solvent was used. It is a rapid, environmentally friendly safe method, and could be applied for routine enantiomeric analysis of PMMA and MDMA in the pharmaceutical industry, forensic science, and environmental analysis.