Background Ophthalmic gel has been developed to increase the drug concentration in aqueous humor and to retard the loss of drug from the conjunctival sac. The research was to compare the drug concentration in aqueous humor of cataract patients administered 0.3% gatifloxacin ophthalmic gel with that in patients administered 0.3% gatifloxacin ophthalmic solution. Methods Ninety-six patients with cataract (96 eyes) were randomly assigned to 8 groups. The patients in groups 1-4 received topical gatifloxacin 0.3% ophthalmic gel and those in groups 5-8 received gatifloxacin 0.3% ophthalmic solution. The dose regimen was 1 drop, 4 times a day for 3 consecutive days prior to cataract surgery. On the day of surgery, 1 drop was applied at 15, 30, 60 or 120 minutes before commencement of cataract surgery in groups 1 and 5, groups 2 and 6, goups 3 and 7, and groups 4 and 8, respectively. Aqueous humor was extracted during the cataract surgery for the analysis of gatifloxacin concentration.. Results The concentrations of gatifloxacin in aqueous humor were (0.24 +/- 0.25) mu g/ml, (1.11 +/- 0.74) mu g/ml, (2.32 +/- 2.01) mu g/ml and (1.85 +/- 1.14) mu g/ml in groups 1 to 4, and (0.161-0.25) mu g/ml, (0.31 +/- 0.24) mu g/ml, (0.75 +/- 0.28) mu g/ml and (0.33 +/- 0.22) mu g/ml in groups 5 to 8, respectively. Patients receiving gatifloxacin ophthalmic gel showed greater mean values of gatifloxacin concentration in aqueous humor than those receiving gatifloxacin solution, and such differences were significant with P<0.05 for all comparisons except that between groups 1 and 5. Conclusion Topical gatifloxacin ophthalmic gel can attain significantly greater drug concentrations in human aqueous humor than gatifloxacin ophthalmic solution. Chin Med J 2010;123(15):2105-2110