OBJECTIVES: Fluoroquinolones are broad-spectrum antibiotics commonly used in the treatment of respiratory tract infections, uncomplicated urinary tract infections and gastrointestinal infections. This study described and analyzes trends in the utilization, spending, and average per-prescription cost of fluoroquinolones individually and overall, by the Medicaid programs from 1991 to 2013. METHODS: A retrospective, descriptive analysis was performed using the publicly available national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Service.  Study drugs included ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin, as well as recently withdrawn drugs, grepafloxacin (1999), sparfloxacin (2001), trovafloxacin (2001), and gatifloxacin  (2006).   Annual prescription counts and reimbursement amounts were calculated for all fluoroquinolones reimbursed by Medicaid. Average per-prescription spending as a proxy for drug price was calculated (estimated) for all generic and brand drugs by dividing reimbursement by the number of prescription. RESULTS: The total number of fluoroquinolone prescriptions rose 340% from 1.66 million in1991 to 5.65 million in 2005, and then decreased to 4.21 million in 2013. Total expenditures on fluoroquinolones increased from $81 million in 1991 to $395 million in 2004, and then decreased to $163 million in 2013. The average pre-prescription price for generic ciprofloxacin was $7.76 in 2013, whereas the price per-prescription of branded (Cipro) ciprofloxacin was $149.34. The sharp decrease in the utilization of Trovan can be explained by the withdrawal from the market in 2001 because of risk of liver failure. CONCLUSIONS: Increased expenditures for fluoroquinolones paralleled with increased utilization.  Generic drug utilization increased dramatically after brand-name patent expiration.  Fluoroquinolone drug utilization might be also associated with its safety profile and related disease treatment guidelines.