To investigate clinical outcomes of vitrectomy for intractable diabetic macular edema (DME) in which anti-vascular endothelial growth factor (anti-VEGF) agents or periocular steroid were not effective. This retrospective study examined 27 eyes of 25 cases. The main measurements included changes in visual acuity (VA) and retinal morphology. Vitrectomies were performed using the Constellation System 25G. Prior to undergoing vitrectomy, patients were treated with anti-VEGF agents or periocular injection of triamcinolone acetonide. The average number of anti-VEGF agent injections was 3.1 ± 2.8. Triamcinolone was used in 15 eyes. There was no significant change in the mean logMAR best-corrected visual acuity (BCVA) between baseline and posttreatment, with values of 0.49 ± 0.29 and 0.55 ± 0.33, respectively (P = 0.31). Compared with preoperative BCVA, postoperative BCVA improved by more than two lines in 4 eyes (14%), remained the same in 17 eyes (63%), and decreased in 6 eyes (23%). Morphologically, retinal thickness improved by more than 50μm in 16 eyes (59%), remained unchanged in 7 eyes (26%), and increased in 5 eyes (18%). Retinal edema resolved in all of the cases in which macular epiretinal membrane (ERM) or vitreomacular traction (VMT) was detected by optical coherence tomography during pretreatment. Vitrectomy can potentially stabilize the retinal morphology in intractable DME and is likely more effective in DME cases accompanied by ERM or VMT.