Methamphetamine (meth) from meth syntheses or habitual meth smoking deposited on household surfaces poses human health hazards. The U.S. State Departments of Health require decontamination of sites where meth was synthesized (meth labs) before they are sold. National Institute for Occupational Safety and Health (NIOSH) methods for meth analysis require wipe sampling, extraction, clean-up, solvent exchange, derivatization, and/or mass spectral analysis using selected ion monitoring. Rapid and inexpensive analyses could screen for drug-contamination within structures with greater spatial resolution, provide real-time analyses during decontamination, and provide thorough documentation of successful clean ups. Herein an autosampler/open-air ion source time-of-flight mass spectrometric technique is described that required only direct sampling using cotton-swab wipes. Each wipe sample collection required 2 min and data acquisition required only 13 s per sample. Optimum collision-induced dissociation voltages, desorption gas temperatures, and wipe sample solvents were determined for 11 drugs. Peaks were observed in analyte-ion traces for 0.025 µg/100 cm2 of meth and seven other drugs. This level is half the detection limit of NIOSH methods and one-fourth of the lowest U.S. state decontamination limit for meth. Dynamic ranges of 100 in concentration were demonstrated for eight drugs, which is sufficient for a screening technique. The volatilities of 11 drugs deposited on glass were determined. The pick up of the drugs by solvent-soaked cotton-swab wipes from glass relative to acrylic latex paint was also compared. Published in 2011 by John Wiley & Sons, Ltd.