Rates of fluoroquinolone resistance among Pseudomonas aeruginosa in hospitals are increasing, but interhospital variability is great. We sought to determine whether this variability correlated to fluoroquinolone use in hospitals and in the surrounding community. Hospital quinolone use in 1999 (24 hospitals) through 2001 (35 hospitals) was determined from billing records. The number of fluoroquinolone prescriptions within a 10-mile (approximately 16-km) radius of each hospital was determined for 1999 and 2000. Hospital fluoroquinolone use increased from 1999 through 2001, from 137 to 163 defined daily doses (DDD)/1000 patient-days (P=.01). The rate of community fluoroquinolone use also increased, from 2.3 to 2.8 DDD/1000 inhabitant-days (P<.001). Rates of fluoroquinolone-resistant P. aeruginosa increased from 29% in 1999 to 36% in 2001 (P=.003). Both community and hospital fluoroquinolone use were predictive of rates of fluoroquinolone-resistant P. aeruginosa. Levofloxacin was associated with resistance, but ciprofloxacin was not. Most of the variability in resistance rates is explained by volume of fluoroquinolone use, both in the hospital and the surrounding community.