Antibiotic resistance in the longterm-care facility (LTCF) setting is of increasing concern due to both the increased morbidity and mortality related to infections in this debilitated population and the potential for transfer of resistant organisms to other healthcare settings. Longitudinal trends in antibiotic resistance in LTCFs have not been well described. Correlational longitudinal survey study. Four LTCFs in Pennsylvania. All clinical cultures of residents of the participating LTCFs (700 total beds) from 1998 through 2003. We assessed the annual prevalence of resistance to various antimicrobials of interest for the following organisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and enterococcus species. A total of 4,954 clinical isolates were obtained during the study. A high prevalence of antimicrobial resistance was noted for many organism-drug combinations. This was especially true for fluoroquinolone susceptibility among the Enterobacteriaceae (susceptibility range, 51.3% to 92.2%). In addition, the prevalence of resistance to various agents differed significantly across study sites. Finally, significant increasing trends in resistance were noted over time and were most pronounced for fluoroquinolone susceptibility among the Enterobacteriaceae. The prevalence of antimicrobial resistance has increased significantly in LTCFs, although trends have varied substantially across different institutions. These trends have been particularly pronounced for fluoroquinolone resistance among the Enterobacteriaceae. These findings demonstrate that antimicrobial resistance is widespread and increasing in LTCFs, highlighting the need for future studies to more clearly elucidate the risk factors for, and potential interventions against, emerging resistance in these settings.