Aristolochia clematitis L. is a perennial herbaceous plant distributed throughout Europe, Asia Minor and Caucasus. It has been used as a medicinal plant since antiquity but not in recent times because it contains poisonous aristolochic acid, causing progressive kidney failure. The aim of this work was to study Aristolochia clematitis ecology on the basis of vegetation plots from the European Vegetation Archive, and to investigate the differentiation of its ecological niche using a co-occurrence-based measure of ecological specialization (ESI). The ecological niche was studied on three spatial scales: on the entire distribution area, its differentiation across 200 × 200 km grid cells and the differences between three central and three marginal regions. Our results suggest that Aristolochia clematitis has a very broad ecological niche occurring in a range of different habitats and climatic conditions, with a trend of a niche width decrease with the distance from the geographical center. The plant prefers more stable communities with less anthropogenic influence moving towards the margin of the distribution area. Specialization towards the marginal area is a result of evolutionary history, which refers to the recent anthropogenically induced spread from its original home range. A high incidence of Aristolochia clematitis in the vegetation of arable lands and market gardens as well as anthropogenic herbaceous vegetation in the distribution center corresponds to the geographical incidence of Balkan Endemic Nephropathy.