Novel water soluble polymer complexes of bendamustine hydrochloride, a bifunctional alkylating agent with antimetabolic and cytotoxic activity, were developed using biodegradable polymer carriers—poly(oxyethylene H-phosphonate), poly(methyloxyethylene phosphate) and poly(hydroxyoxyethylene phosphate). Bendamustine hydrochloride was immobilized onto polyphosphoesters via covalent, ionic and hydrogen bonding. The structure of the complexes formed was elucidated by 1H, 13C, 31P NMR and FT-IR spectroscopy. The chemical stability of bendamustine hydrochloride in the novel complexes was studied by HPLC analysis based on a validated method with appointed analytical parameters such as specificity, repeatability, limit of quantitation, limit of detection and linearity. The results from the HPLC indicate that in neutral (pH 7) and alkaline (pH 9) media bendamustine hydrochloride in the polymer complexes is more stable than the pure bendamustine hydrochloride. The enhanced stability of the immobilized drug is explained with the drug interaction with the polymer carriers or their degradation products.