The study shows potential applications of (E)-azastilbene derivatives with antimicrobial properties for surface water protection. Four derivatives of (E)-azastilbene under study interact with nine different microorganisms. The research was carried out using samples of surface waters collected from three rivers: the Bug, the Liwiec and the Muchawka. The Muchawka River flows into the Liwiec River, which, in turn, is a tributary of the Bug River. During the study, short- and long-term stability of selected stilbene derivatives in collected surface water samples was determined. The extraction process was carried out on a naphthylpropyl extraction column with a recovery rate of about 95%. The highest average reduction in the stability of the analysed derivatives after 12 months was found in water samples collected from the Muchawka River and amounted to 59%, whereas the smallest average reduction of 47% was found in water samples from the Liwiec River.