This retrospective, consecutive interventional study investigated the long-term clinical outcomes of combined vitrectomy with intraoperative dexamethasone implants for non-tractional refractory diabetic macular edema (DME). The study included 43 eyes from 39 participants with DME that had continued for more than 6 months despite repeated non-surgical treatment. Postoperative changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated over 3 years. A Kaplan-Meier curve was obtained for any additional non-surgical treatment, and the average number of non-surgical treatments required for DME before and after surgery was compared. Other postsurgical complications were also investigated. The logMAR BCVA improved from 0.526 ± 0.417 (20/67) preoperatively to 0.294 ± 0.374 (20/39) 3 years postoperatively (p < 0.001, generalized estimating equation). The CMT improved from 478 ± 122 μm preoperatively to 314 ± 90 μm 3 years postoperatively (p < 0.001, generalized estimating equation). Additional non-surgical treatment was not required for 29 (67%) eyes. The average number of annual non-surgical treatments decreased from 5.04 times preoperatively to 0.34 times postoperatively. Seventeen (40%) eyes developed temporary ocular hypertension after surgery, which normalized after antihypertensive eye drop instillation. In conclusion, vitrectomy combined with intraoperative dexamethasone implantation provides satisfactory long-term clinical outcomes for non-tractional refractory DME while reducing the number of intraocular injections for DME.