The feasibility of an electrospray coupled with a ⁶³Ni-differential ion mobility spectrometer (DMS) for the analysis of water samples was proven on examples of 2-hexanone, fluoroacetamide, L-nicotine and 1-phenyl-2-thiourea water solutions. The model substances were selected in order to cover the vapor pressure range of 0.3 – 1467 Pa. To reduce the inline humidity, which demonstrates a strong influence on the analyte compensation voltage, two units with a desolvation region lengths of 15.5 and 7 mm were examined. The counter gas (heated to 100 °C nitrogen) with flow rates of 100 mL min⁻¹ and 30 mL min⁻¹ for short and long desolvation units, respectively, was essential for the efficient reduction of humidity. The reduction of water content in the carrier gas to 2.2 – 2.4 g m⁻³ and to 1.8 – 2.0 g m⁻³ for the short and long desolvation unit, respectively, was achieved at an electrospray flow rate of 1000 nL min⁻¹. With this adjusted experimental setup, the detection of model substances in the water solutions, in the range of 0.1 – 50 mg L⁻¹, was performed. No correlation between the vapor pressure and signal area was observed. The high stability of the inline humidity, and the correspondingly stable carrier gas flow rate, were found to be essential for an acceptable reproducibility.