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Abstract Background Tigecycline is a novel antibiotic with activity against multidrug resistant bacteria. The aim of this study was to assess the efficacy of tigecycline use in serious hospital-acquired infections (HAI) Case presentation Prospective observational study of tigecycline use was conducted in a 1500 beds university hospital. From January 1, 2007 and January 31, 2010, 207 pts were treated with tigecycline for the following indications: intra-abdominal, pneumonia, bloodstream and complicated skin and soft tissue infections and febrile neutropenia. The therapy was targeted in 130/207 (63%) and empirical in 77/207 (37%) patients. All bacteria treated were susceptible to tigecycline. Median duration of tigecycline therapy was 13 days (range, 6-28). Clinical success was obtained in 151/207 (73%) cases, with the highest success rate recorded in intra-abdominal infections [81/99 (82%)]. Microbiological success was achieved in 100/129 (78%) treated patients. Adverse clinical events were seen in 16/207 patients (7.7%): Conclusions Considering the lack of data on tigecycline for critically ill patients, we think that the reported data of our clinical experience despite some limitations can be useful for clinicians.