To identify characteristics associated with cataract occurring during the course of Acanthamoeba keratitis. Retrospective observational case series. Eighty-one laboratory-confirmed patients with Acanthamoeba keratitis. Review of clinical records. Development of cataract during management of Acanthamoeba keratitis. Rapidly progressive crystalline lens opacification occurred in 9 eyes within 4 to 15 weeks after diagnosis of Acanthamoeba keratitis. Three were associated with inflammatory complications, including anterior scleritis (2 eyes) and iridocyclitis (1 eye). Six others had the abrupt onset of a dense cataract, including 5 with iris atrophy, that occurred during the initial 6 months of therapy with chlorhexidine, a diamidine, and adjunctive corticosteroid. Extracapsular cataract extraction was performed with or after penetrating keratoplasty. Secondary glaucoma developed in 6 of 9 eyes subsequent to iris atrophy (4 eyes) or a cyclitic membrane (2 eyes), and 3 eyes underwent trabeculectomy. Cataract may occur and progress during the management of Acanthamoeba keratitis in association with anterior segment inflammation, iris atrophy, and secondary glaucoma.