A preliminary field evaluation of a second-generation handheld oral fluid testing device, the Alere DDS2 Mobile Test System (DDS2), is described. As part of a larger study, drivers were randomly stopped at various locations across California (in 2012) and asked to submit voluntarily to a questionnaire regarding their drug and alcohol use, a breath alcohol test and collection of oral fluid with the Quantisal device. The Quantisal-collected oral fluid samples were sent for laboratory-based analyses. At one location, 50 drivers were asked to submit an additional oral fluid sample using the DDS2 collection device; these samples were analyzed by using the DDS2 mobile test system. Thirty-eight donors (76%) provided specimens that were successfully run on the mobile system; in 12 cases (24%), the device failed to provide a valid result. Thirty-two of the 38 collected samples were negative for all drugs; five were positive for tetrahydrocannabinol and one was positive for methamphetamine using the mobile device. These results corresponded exactly with the laboratory-based results from the Quantisal oral fluid collection.