Purpose: To compare the functional and anatomical outcomes after a 0.2 µg/day fluocinolone acetonide (FAc) implant between vitrectomized and nonvitrectomized eyes with chronic diabetic macular edema (DME). Methods: This is a retrospective, comparative analysis of 43 eyes with chronic DME. All eyes were treated with a single 0.2 µg/day FAc implant and followed up for a mean period of 8.5 months (median, 6.0 months; range, 1-21 months). The patients with a 0.2 µg/day FAc implant were divided into 2 groups: 24 eyes which had undergone pars plana vitrectomy prior to 0.2 µg/day FAc (group 1) and 19 eyes which had not been vitrectomized (group 2). Outcome measures included mean changes in best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, central subfield foveal thickness (CSFT), and intraocular pressure (IOP), and were measured prior to administration of the 0.2 µg FAc implant, in the first week, at month 1, and quarterly thereafter. Results: Following the 0.2 μg/day FAc implant, the mean change in BCVA at the last observation point, from baseline, was +16.9 ± 3.39 (mean ± SE) letters (p ≤ 0.001) in group 1 and +8.2 ± 4.62 letters (p = 0.092) in group 2. From baseline, a gain of ≥15 letters was achieved in 37.5 and 36.8% of the eyes in group 1 and group 2, respectively. Additionally, an improvement in vision ≥20/40 in 29.2% of group 1 and 15.8% of group 2 was observed. The mean change in CSFT was -217.7 ± 40.8 µm and -155.6 ± 43.4 µm in group 1 and group 2, respectively. The mean change in IOP was +1.6 ± 0.7 mm Hg in group 1 and +0.8 ± 1.3 mm Hg in group 2, relative to baseline. At the last observation point, there were no significant differences between groups 1 and 2 (p > 0.05) in terms of their changes in BCVA, CSFT, and IOP. Conclusion: The results from the real-life practice study demonstrate that the 0.2 μg/day FAc implant is effective and well tolerated in vitrectomized and nonvitrectomized eyes of patients with chronic DME. Our results support the use of a 0.2 μg/day FAc implant to obtain long-term functional and anatomical improvements (mean, 8.5 months; median, 6.0 months) in vitrectomized and nonvitrectomized eyes.