A lyophilized bendamustine composition consisting of bendamustine hydrochloride, an aqueous solvent, and optionally an excipient, and a method of preparation thereof for treating a condition in a subject are provided. The aqueous solvent includes, for example, water, an acid, a base, or a salt, etc. The excipient includes at least one cryoprotectant, for example, sucrose, trehalose, mannitol, etc. A pre-lyophilization bendamustine composition is lyophilized, for example, by freezing, primary drying, annealing, secondary drying, condensed cooling and evacuation at preset temperatures to obtain the lyophilized bendamustine composition as a cake, a powder, or a solid concentrate. The lyophilized bendamustine composition is free of a non-aqueous solvent. Reconstitution is performed by mixing the lyophilized bendamustine composition with an aqueous solvent for about 30 seconds to 300 seconds. The reconstituted bendamustine product containing about 0.2 wt % to about 2.5 wt % by weight of impurities is administered to the subject in need thereof.
