Purpose To report a case of culture-positive endophthalmitis after intravitreal injection of bevacizumab (Avastin) resulting in a devastating visual outcome. Method A retrospective case report of a 51-year-old diabetic women who presented with further decrease in her vision, redness, and mild pain in her eye 3 days after intravitreal injection of Avastin for macular edema due to a branch retinal vein occlusion. Results Clinical diagnosis of endophthalmitis was made and, after obtaining a vitreous tap, intravitreal antibiotics were administered. Because of worsening of the endophthalmitis, pars plana vitrectomy was undertaken followed by repeat intravitreal antibiotics injection. The patient’s ocular condition improved dramatically; however, her visual acuity did not improve. The cultures from vitreous taps revealed Staphylococcus lugdunesis. Conclusion Intravitreal injection of Avastin may be associated with a risk of S. lugdunesis-caused endophthalmitis which can have a devastating effect on the final visual outcome.