Display omitted •Tobacco waste – material which contain important active compounds.•Striking differences between tobacco waste and leaves.•With SWE a considerable amount of extracted active compound can be achieved.•Production of some unwanted compounds can be avoided with proper optimization of SWE process. Three fraction of tobacco waste (scrap, midrib and dust) were subjected to subcritical water in a wide temperature range (150–250 °C), using solvent-solid ratio (10–30 mL/g) for periods from 5 to 25 min in a batch reactor and compared with tobacco leaves to determine the changes in content of compounds during tobacco processing. Optimal extraction conditions were established using RSM. Depending on applied extraction conditions as well as waste fraction, different concentrations of active compounds were determined. Tobacco waste extracts were characterized with high level of nicotine from 0.907 to 4.610%, and considerable amounts of 3,4 DHBA from 0.118 to 1.249%, chlorogenic acid from 0.033 to 0.507% and rutin up to 0.874%. Moreover, in all extracts some tobacco specific compounds were detected, namely nicotinic acid 0.087-0.846% and nicotinamide 0.095-0.400% as a product of nicotine hydrothermal degradation. At higher temperatures the presence of 5-HMF, furfural and 5-MF was detected.