AIM: To investigate the change of diabetic macular edema (DME) post vitrectomy and its risk factors. METHODS: This retrospective study included 365 eyes of 330 patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) with gradable optical coherence tomography (OCT) imaging from January 2018 to March 2022. The incidence of post vitrectomy DME (PV-DME) was defined as patients with a central retinal thickness (CRT) >300 µm by OCT among patients without preoperative DME. RESULTS: The cumulative incidence of PV-DME at 3mo was 40.1% (89/222), with its majority subtype of single diffused retinal thickening (66.2%) followed by single cystoid macular edema (27.0%). Multivariate Cox regression analysis indicated that a thicker preoperative CRT [hazard ratio (HR)=1.01, 95% confidence interval (CI) 1.00-1.02] and intraoperative internal limiting membrane peeling (HR=3.18, 95%CI 1.85-5.47) were associated with the presence of PV-DME, while intraoperative intravitreal injection of triamcinolone acetonide (HR=0.28, 95%CI 0.13-0.57) was protective against PV-DME. In eyes with preoperative DME (n=143), the CRT decreased gradually from 468.3±177.7 μm preoperatively to 409.5±151.0 μm (P=0.027), 377.4±141.9 μm (P<0.001), and 368.0±157.6 μm (P<0.001) at 7d, 1 and 3mo postoperatively, respectively. Multivariate linear regression analysis indicated that only a thicker preoperative CRT (β=0.77, 95%CI 0.63-0.92) was associated with a decreasing postoperative CRT. CONCLUSION: PV-DME is a very common postoperative complication in patients with PDR. Triamcinolone acetonide could prevent its formation. Attention should be paid to patients with a thicker preoperative CRT and internal limiting membrane peeling.