Oral fluid (OF) is potentially useful to detect driving under the influence of drugs because of its ease of sampling. While cannabis is the most prevalent drug in Europe, sensitivity issues for Δ(9) -tetrahydrocannabinol (THC) screening and problems during OF collection are observed. The ability of a recently improved OF screening device - the DrugWipe5S(®) , to detect recent THC use in chronic cannabis smokers, was studied. Ten subjects participated in a double-blind placebo-controlled study. The subjects smoked two subsequent doses of THC; 300 µg/kg and 150 µg/kg with a pause of 75 min using a Volcano vapourizer. DrugWipe5S(®) screening and OF collection using the Quantisal™ device were performed at baseline, 5 min after each administration and 80 min after the last inhalation. Blood samples were drawn simultaneously. The screening devices (n = 80) were evaluated visually after 8 min, while the corresponding OF and serum samples were analyzed respectively with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) or gas chromatography-mass spectrometry (GC-MS). Neat OF THC concentrations ranged from 12 361 ng/g 5 min after smoking down to 34 ng/g 80 min later. Under placebo conditions, a median THC concentration of 8 ng/g OF (0-746 ng/g) and < 1 ng/ mL serum (0-7.8 ng/mL) was observed. The DrugWipe5S(®) was positive just after smoking (90%); however, sensitivity rapidly decreased within 1.5 h (50%). Sensitivity of DrugWipe5S(®) should be improved. As chronic cannabis users have high residual THC concentrations in their serum and OF, confirmation cut-offs should be set according to the aim of detecting recent drug use or establishing zero tolerance.