There is no consensus on the antibiotic therapy for bone infection due to the heterogeneous spectrum of diseases. Most authors suggest different durations of treatment based on pathophysiological considerations. However, adverse effects are related, at least in part, to the duration of treatment. We, therefore, investigated a 6 weeks antibiotic combination therapy for all cases of bone infection. Herewith, we report the results of this therapeutic approach. This is a cohort study including all patients presenting with bone infection, regardless of the mechanism involved. The diagnosis was based on bone biopsy obtained through invasive procedures. Chronic bone infection was defined as a history of disease of over 1 month duration. The duration of clinical follow-up following treatment discontinuation was at least 6 months. Cured bone infection was defined as the absence of relapse after antibiotic discontinuation. One hundred and eighteen patients were included between July 2005 and March 2009; 61 presented with bone infection following prosthetic implant (52%) and the 57 remaining patients had bone infection without foreign material (48%). Surgery was required for 80 patients (68%). Microbial agents were identified in 116/118 patients, with 24 patients presenting with polymicrobial sepsis (20%). The mean duration of antibiotic treatment was 42 +/- 0.2 days and the mean clinical follow-up was 27 +/- 14 months. The treatment success rate was 91.5% (108/118). Six weeks of antimicrobial therapy appears to be effective for nearly all bone infections, regardless of the pathophysiology. These results encourage us to pursue attempts to simplify the management of bone infection without obvious prejudice to the patient.