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Acanthamoeba keratitis is a rare, vision-threatening disease. Commercially available antiamoebics are poorly cysticidal and highly toxic, and therapeutic keratoplasties can be complicated by recurrence or graft failure. We aimed to discuss the use of oral miltefosine for treatment of recalcitrant Acanthamoeba keratitis.A 44-year-old contact lens wearer presented with a 2-week history of red painful eye and decreasing vision. After poorly responding to topical corticosteroid on the presumptive diagnosis of anterior uveitis, she developed radial keratoneuritis. Corneal scraping was positive for Acanthamoeba. No clinical response to treatment was observed with topical chlorhexidine 0.02%, polyhexamethylene biguanide 0.02%, and oral voriconazole. She then underwent 2 therapeutic keratoplasties with prompt recurrence of the disease in the keratoplasty graft.Oral miltefosine was added to the treatment. She underwent a third penetrating keratoplasty 8 months later. The excised button was negative for amoeba. She continued miltefosine for 3 more months. No recurrence was observed after 30 months.This case shows resolution of recalcitrant Acanthamoeba keratitis with oral miltefosine in an immunocompetent patient. Further clinical evidence would be needed to possibly incorporate this medication in the antiamoebic armamentarium.