Purpose. To report the acute development of hypopyon after primary cryopreserved amniotic membrane transplantation (AMT) for persistent corneal epithelial defect and sterile ulceration. Case Presentation. A selected case report of a 71-year-old male who underwent primary cryopreserved AMT for the management of long-standing corneal epithelial defects and stroma thinning. The patient developed 2 mm sterile hypopyon within 48 hours after AMT for corneal surface reconstruction. He responded well to the intensified routine postoperative topical treatment of steroid and antibiotic eye drops with the hypopyon resolving completely one week later. Five weeks after surgery, the corneal surface was smooth and epithelialized with no anterior chamber reaction or recurrence of hypopyon. Discussion. Hypopyon may develop as a rare complication of primary cryopreserved AMT for sterile corneal defects. It may be attributed to immunologic or hypersensitivity reaction and should be differentiated from active ocular infection as it resolves spontaneously with the routine postoperative topical treatment of steroid and antibiotic drops.