This paper explores the possibility of using biodegradable cross-linked gelatines as antibiotic devices for a long-term elution (80 days). Capillary electrophoresis (CE) has been utilized to evaluate the mass percentage of vancomycin and gelatine contemporary released from differently cross-linked vancomycin loaded gelatine samples in an elution time ranging from 24 to 1920 h. While the solubilization kinetic of gelatine samples differently cross-linked can be very close described by the simplified Higuchi model, the vancomycin release kinetic is contemporary governed by both the Fickian diffusion process trough the gelatine matrix network and the dissolution process of the matrix due to its degradation. Comparing the antibiotic eluting kinetics from gelatine at diverse cross-linking degree we observed that the degradation of the proteic matrix appears to have a minor influence in the drug release control. Vancomycin released from all the gelatine partially cross-linked samples results active against Staphylococcus aureus and Streptococcus faecalis which represent the most pathogens commonly isolated in orthopaedic infections. Vancomycin overcomes the minimum inhibitory concentration for both the bacteria in the whole range of elution time. Cross-linked gelatine devices appear to represent a useful biodegradable delivery system for local anti-infective therapy in arthoplasty.