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Purpose: To determine any changes in macular or choroidal thickness associated with the use of intracameral moxifloxacin as postcataract endophthalmitis prophylaxis. Setting: University of Campinas, Campinas, São Paulo, Brazil. Design: Prospective, randomized, partially masked, single-site clinical trial. Methods: Phacoemulsification surgery patients in the experimental group (Group A) received a 0.03 mL intracameral injection of undiluted moxifloxacin from a sealed bottle immediately after phacoemulsification surgery (150 μg in 0.03 mL—Vigamox solution), whereas the control group (Group B) did not. Investigators evaluated in masked fashion macular and choroidal thickness using spectral-domain optical coherence tomography preoperatively and postoperatively. Results: A total of 93 patients were included (48 in Group A and 45 in Group B). Baseline parameters were similar between the groups. Either of the 2 parameters assessed differed statistically between the groups or preoperatively vs postoperatively. On postoperative day 30, central macular thickness was 8.85 ± 14.78 μm in Group A and 10.26 ± 22.44 μm in Group B (P = .7232); choroidal thickness as measured by enhanced depth imaging (EDI) was 1.45 ± 16.13 μm in Group A and 3.74 ± 16.15 in Group B (P = .5017). On postoperative day 60, central macular thickness was 19.53 ± 39.28 μm in Group A and 17.14 ± 53.68 μm in Group B (P = .8363); EDI was 5.08 ± 21.96 μm in Group A and 5.24 ± 15.8 in Group B (P = .9752). Conclusions: The application of intracameral injection of 0.03 mL of undiluted 0.5% moxifloxacin during phacoemulsification surgery as endophthalmitis prophylaxis induced no changes in macular or choroidal thickness.