Methicillin-resistant Staphylococcus aureus (MRSA) which exhibits a worldwide spread, has become a serious public health problem. There are several studies indicating that there may be a relationship between the high rate of MRSA infections and long-term use of fluoroquinolones. The aim of this study was to investigate the effect of fluoroquinolone (FQ) use in the respiratory intensive care unit (ICU) on the development of the hospital-acquired MRSA infection and mortality. This was a single center experience, in which the clinical and laboratory data of the patients who were hospitalized in the respiratory ICU for two years, were retrospectively evaluated. The relationship between FQ use and the development of MRSA infection was evaluated with correlation analysis, and its relationship with the mortality was evaluated with regression analysis. A total of 302 patients were included in the study and 93 (30.7%) of them were found to be treated with FQs. Sixty-four of those 93 patients were male and the mean age was 71.1 +/- 12.5 years. During the follow-up, MRSA infections developed in 11.9% (36/302) of the patients, and the rate of MRSA infection in FQ using patients was 15.1% (14/93), of them eight were ventilator-associated pneumonia (VAP) and six were secondary bacteremia. Although a positive correlation was found between FQ use and the development of MRSA infection, it was not statistically significant [P=0.521 (Spearman), p=0.037 (Pearson)]. In addition cut-off values for CRP and leukocyte counts, which were checked when a patient with FQ use admitted to the ICU, were determined as 7.85 mg/L and 7.650/mm(3), respectively. The analysis of the relationship between CRP, leukocyte counts and the development of MRSA infection revealed a statistically significant positive relationship between high leukocyte levels (>7.650/mm(3)) and the development of MRSA infection (P=0.017, p=0.246), but no such relationship for the CRP levels (P=0.121, p=0.178). The mortality rate in patients with FQ use was found as 42% (39/93), and it was determined that malignancy, history of admission to hospital in the previous six months and the presence of a hospital-acquired infection increased the risk of mortality (p=0.020, p=0.038 and p=0.024, respectively). In the multivariate analysis, four independent risk factors related to the mortality in patients under FQ treatment were determined, namely malignancy (OR: 2.280, p=0.002), re-intubation practices (OR: 4.071, p=0.005), VAP (OR: 5.097, p=0.009) and the use of FQ > 7 days (OR: 3.63, p=0.003). In conclusion, our data indicated that the use of FQs in the ICU did not increase the development of hospital-acquired MRSA infection significantly, and FQ use for more than seven days was an independent risk factor for mortality. Additionally, it was thought that high leukocyte counts might be a predictive marker for the development of MRSA infection.