Solid-phase extraction (SPE) is becoming a commonly used extraction technique. Most existing SPE methods extract a single drug from a relatively clean biological matrix (e.g., plasma, serum, or urine) using a silica-based column. These methods, however, are generally not satisfactory for forensic applications because the majority of biological samples are not as clean (e.g., whole blood, bile, tissues). Silica-based columns also may have reproducibility and stability problems. Polymer-based columns have been developed to overcome some of these limitations. In this study, sequential extraction of acidic, neutral, and basic drugs from whole blood using a polymer-based column, Oasis MCX, was undertaken. The extraction procedure developed involved a conditioning step using methanol followed by water; a three-step wash sequence using water, 0.1 M hydrochloric acid, then water/methanol (95:5); and two elution steps. One elution step was for acidic and neutral drugs utilizing acetone/chloroform (1:1), and a second used ethyl acetate/ammonium hydroxide (98:2) for basic drugs. Of the drugs tested, 75% were extractable from whole blood and detectable at therapeutic concentrations. Good recoveries and clean extracts were achieved for the basic drugs; however, the extracts were not as clean for acidic drugs. Unfortunately, the Oasis MCX procedure was not suitable for extracting all drugs (e.g., benzodiazepines).