PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral administration. DESIGN: Prospective, nonrandomized clinical series. METHODS: Twenty-four patients (mean age = 62.8 years) undergoing elective pars plana vitrectomy were assigned to a dosing group: control (n = 3), which received no medication; single-dose (n = 11), which received one 400 mg oral dose of moxifloxacin 3 hours before surgery; and five-dose (n = 10), which received one 400 mg dose on each of the 4 days preceding surgery and a fifth dose 3 hours before surgery. Vitreous samples were obtained and analyzed. RESULTS: Control, below quantifiable levels; single-dose, 0.572 +/- 0.239 microg/mL; and five-dose, 1.200 +/- 0.645 microg/mL. CONCLUSIONS: Five doses of oral moxifloxacin lead to higher intravitreal drug concentrations than single-dose administration. Both regimens, however, achieve levels that exceed the MIC90 of many bacteria implicated in postoperative endophthalmitis.