Designer psychostimulants are known by recreational drug users to produce a complex array of adrenergic and hallucinogenic effects. Many of these drugs are not targeted during routine toxicology testing and as a consequence, they are rarely reported. The purpose of this study was to develop a procedure for the detection of 15 psychostimulants in urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS), specifically 2,5-dimethoxy-4-bromophenethylamine (2C-B), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,5-dimethoxy-4-methylphenethylamine (2C-D), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxyphenethylamine (2C-H), 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-chloroamphetamine (DOC), 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4-methylamphetamine (DOM), and 4-methylthioamphetamine (4-MTA). Analytical recoveries using solid-phase extraction were 64-92% and the limit of detection was 0.5 ng/mL for all drugs except 2C-B (1 ng/mL). The assay was evaluated in terms of analytical recovery, precision, accuracy, linearity, matrix effect, and interferences. The technique allows for the simultaneous detection of 15 psychostimulants at sub-ng/mL concentrations.