Endophthalmitis in postoperative silicone oil-filled eyes is rare. The traditional management of these eyes is a return to the operating room for oil removal, instillation of intravitreal antibiotics, and reinjection of silicone oil. We describe 2 cases of endophthalmitis successfully treated with an office injection of intravitreal antibiotics. In both eyes, there was a prompt resolution of endophthalmitis with no apparent signs of retinal toxicity and with favorable visual outcomes. These are the first cases to be described of endophthalmitis in silicone oil-filled eyes successfully treated with intravitreal antibiotics alone.