Purpose: We report on three patients who received 0.625% povidone-iodine (PVI) intravitreal injections to treat endophthalmitis that did not respond to conventional antibiotic treatment or were inoperable.Case summary: Case 1 was a 42-year-old female with suspected left-eye endophthalmitis that developed after anterior chamber irrigation to treat silicone oil emulsification. A 0.625% PVI intravitreal injection reduced inflammation of the anterior chamber and the vitreous. Case 2 was an 84-year-old male who was blind in the left eye due to glaucoma. He was diagnosed with endogenous endophthalmitis on the basis of the anterior chamber hypopyon and vitreous inflammation. After 0.625% PVI intravitreal injection, the endophthalmitis resolved without any recurrence. Case 3 was a 49-year-old female with suspected endogenous left-eye endophthalmitis attributable to a liver abscess. Despite intravitreal antibiotic injections, the inflammation worsened. A 0.625% PVI intravitreal injection improved both the anterior chamber and vitreous inflammation.Conclusions: Intravitreal 0.625% PVI injection is a useful option when a patient with endophthalmitis is likely to not recover full vision, when surgery cannot be performed, and when there is no response to empirical antibiotics.