We assessed the adherence to the prescribing hospital protocol for tigecycline and factors associated with noncompliance. A total of 103 patients were included in the study. In 23 (22.3%) patients, tigecycline was not administered according to the protocol, mostly because of the availability of other therapeutic alternatives and prescription for indications that were not included in the guidelines. factors independently associated with nonadherence to the protocol were community-acquired infection (OR, 14.01; 95% CI, 1.54-127.12; P=0.019), and empirical tigecycline treatment (OR, 6.97; 95% CI, 0.88-55.40; P=0.066). penicillin allergy (OR, 0.004; 95% CI, 0.000-0.071; P=0.001) and previous antibiotic treatment (OR, 0.025; 95% CI, 0.003-0.233; P=0.001) were factors associated with adherence to the hospital protocol. A positive time trend between total number of prescriptions and non-compliant prescriptions with the protocol was observed (Spearman's rho coefficient 0.971; P=0.001). Adherence to tigecycline protocol could be improved by focusing on protocols for community-acquired infections, mainly skin and soft tissue infections.