We evaluated a new point-of-care (POC) device for urine drugs of abuse (DOA) screening including appropriate clinical interpretation and potential benefits in a large academic medical center. Two hundred consecutive urine samples were tested using Syva Rapid Test (SRT) and existing laboratory methods (Syva EMIT II). Agreement between methods was acceptable with some considerations. Threshold concentration differences, drug interferences, and cross-reactivity profiles of the class-specific assays resulted in performance differences between the POC and central laboratory methods. Clinical interpretation of POC results requires an understanding of these issues as well as the limitations of urine testing. While urine-based screening is used in workplace testing and in a variety of clinical applications, quantitative blood measurements of some drugs (e.g. ethanol, acetaminophen, salicylate, +/-tricyclic antidepressants) will remain important in the emergent setting. Performance of the SRT method takes approximately 10 min. Consequently, the major advantage over laboratory methods is rapid turnaround time. At the Massachusetts General Hospital, the most important application is for samples from the emergency department (about 1700/year). Each institution should assess its own needs and capabilities with regard to POC versus laboratory-based testing for DOA.