Recent reports from different world regions suggest ocular syphilis is re-emerging, in parallel with an increasing incidence of the systemic infection globally. We conducted a large observational study of 127 persons consecutively treated for ocular syphilis at public medical centers in Brazil over a 2.5-year period ending July 2015. Of 104 individuals serologically tested for human immunodeficiency virus (HIV), 34.6% were positive. Ophthalmological evaluations included measurement of Snellen visual acuity and intraocular pressure, and assessment of inflammation by slit lamp examination and dilated posterior eye examination. Involvements in 214 eyes were anterior (6.1%), intermediate (8.4%), posterior (76.2%) and pan- (8.4%) uveitis, and scleritis (0.9%). Multiple anterior and posterior eye complications were observed, including cataract in the anterior eye (incidence rate, 0.18/eye-year) and epiretinal membrane in the posterior eye (incidence rate, 0.09/eye-year); incidence rates of reduction in best-corrected visual acuity to ≤20/50 and ≤20/200 were 0.10 and 0.06/eye-year, respectively. Rates of complications and visual acuity loss did not differ significantly between HIV- positive and negative individuals. In an era of re-emergence, syphilis has ocular complications that may compromise vision, despite treatment with appropriate anti-microbial drugs.