Aim: To compare the efficacy of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) removal and intravitreal triamcinolone acetonide (IVTA) injection in patients with diabetic macular edema (DME). Methods: This study was a retrospective, comparative, interventional case study examining 14 patients (15 eyes in total) who underwent PPV and ILM removal (vitrectomy group), and 14 patients (14 eyes in total) who were treated with an IVTA injection (triamcinolone group). Main outcome measures were visual acuity and central macular thickness at 1, 3 and 6 months postoperatively. Results: Patients in the vitrectomy group had significantly decreased central macular thicknesses at 1, 3 and 6 months postoperatively (p = 0.001, p = 0.001 and p = 0.002, respectively). The improvement in visual acuity was not significant at 1 month, but it gradually became statistically significant at 3 and 6 months after surgery (p = 0.031 and p = 0.015, respectively). Compared with the triamcinolone group, the vitrectomy group showed a better visual acuity at 6 months after surgery (p = 0.025). Conclusions: PPV combined with ILM removal is a good therapeutic option for improving visual acuity and decreasing macular thickness in DME, and this treatment has a better long-term efficacy than a single IVTA injection.