Objective: In clinical studies to assess alternative tobacco products that heat rather than burn tobacco, a compliance biomarker is needed to detect the additional use of conventional cigarettes. Standard biomarkers of exposure to cigarette smoke constituents seem to be not sensitive enough for this purpose. The aim of this research was to identify and characterize a biomarker specific for combusted tobacco. Methods: 2-cyanoethyl mercapturic acid (CEMA), a metabolite of acrylonitrile, was identified as a candidate compliance biomarker. CEMA was analyzed in 24-hour urine samples retained from a clinical study (#NCT00812279) that assessed a test product that heats rather than burns tobacco. The diagnostic accuracy of three different CEMA analysis variables (concentration [CEMAc], amount excreted in 24 hours [CEMAAe24h], CEMA concentration normalized by urinary creatinine [CEMAcreat]) was evaluated by analyzing the receiver operating characteristics (ROC) curves. The diagnostic accuracy of CEMA variables and standard biomarkers of exposure was compared based on the area under the ROC curves. Results: CEMAcreat and CEMAc were able to differentiate between current smokers of conventional cigarettes and both non-smokers and smokers of the test product with high diagnostic accuracy. The performance of CEMAcreat was slightly better than that of CEMAc. Both CEMA variables performed better than standard biomarkers of exposure. Conclusion: The results suggest that CEMAcreat is a suitable biomarker for assessing product compliance in clinical studies assessing alternative tobacco products and allow recommendation of preliminary thresholds to detect recent use of conventional cigarettes based on CEMAcreat levels. This will be verified in future clinical studies.