OBJECTIVES: This study analyses consumption patterns of fluoroquinolones and documents in vitro resistance of S. pneumoniae to fluoroquinolones in ambulatory care in Belgium. METHODS: Data on fluoroquinolone consumption were derived from IMS Health. Volume of consumption was expressed in terms of the number of defined daily doses per 1,000 inhabitants per day (DID). Consumption was valued at public prices pertaining to the year or month of consumption. Respiratory blood isolates were taken from adults to test in vitro susceptibility of S. pneumoniae to levofloxacin and moxifloxacin. The S. pneumoniae strains were isolated in 15 clinical laboratories throughout Belgium. A hundred blood isolates per year were at random selected from 2004 to 2009. Susceptibility and resistance of S. pneumoniae was expressed using the Clinical and Laboratory Standards Institute breakpoints. RESULTS: Fluoroquinolone consumption increased from 24.1 million € in 1993 to a maximum of 44.4 million € in 2002, and then decreased to 35.0 million € in 2009. The volume of fluoroquinolone consumption has fallen consistently from 3.00 DIDs in 2003 to 2.66 DIDs in 2009. Fluoroquinolones were primarily used to treat urinary tract infections (36% of consumption, volume of 0.95 DIDs) and lower respiratory tract infections (26% of consumption, volume of 0.70 DIDs). The minimum inhibitory concentration (MIC) distribution of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004-2009 and resistance to moxifloxacin and levofloxacin was low (≤1%). Moxifloxacin was the most potent fluoroquinolone available for treatment of S. pneumoniae infections in Belgium with MIC90 of 0.19 mg/L. CONCLUSIONS: The volume of fluoroquinolone use remains well controlled and fluoroquinolones were primarily used in those indications where they have been shown to yield clinical benefit. The use of fluoroquinolones has not led, to date, to an increase in the rate of pneumococcal resistance to fluoroquinolones.