Purpose: To report a rare and challenging case of Acanthamoeba keratitis (AK) in non-contact lens wearer that required multiple therapeutic keratoplasty and succesfully treated with topical anti-parasitic drops. Methods: A twenty-two years old Indonesian man with no history of wearing contact lens came to the hospital with chief complain of whitish spot and foreign body sensation in his left eye.  He washed his eyes with tap water and few days afterwards began to develop redness and severe blurred vision. The visual acuity (VA) was hand movement (HM) with wrong projection, there was corneal ulceration and infiltrate of 8 mm diameter. Therapeutic penetrating keratoplasty (PK) was performed due to nonresponsive corneal infiltrate and development of hypopyon. No sign of endophthalmitis was noted on the posterior part of the eye. Parasitic laboratory culture on non-nutrient agar with E. coli overlay from reinfected corneal graft specimen revealed Acanthamoeba in trophozoites and cysts forms. Patient improved with anti-parasitic propamidine 0.1% eyedrops. Conclusion: Acanthamoeba keratitis should be suspected in cases which fail to respond to antibiotic and/or antifungal medical therapies.