Background: To compare the effectiveness of intravitreal ranibizumab (IVR) injections for the treatment of diabetic macular edema (DME) in eyes with and without previous vitrectomy.Methods: The medical records of 30 eyes (13 vitrectomized, 17 nonvitrectomized) of 28 patients (mean age, 59.0±9.6 years; male to female ratio 1:1) who were diagnosed with DME and had received IVR treatment were reviewed retrospectively. The indications of vitrectomy in 13 vitrectomized eyes were intravitreal hemorrhage (n=8), vitreomacular traction (n=1), and epiretinal membrane (n=4). The best-corrected visual acuity (BCVA), central macular thickness (CMT), and total macular volume (TMV) were measured at baseline and at months 6, 12, 18, and 24 of the follow-up.The number of IVR injections, the duration between diagnosis of DME and IVR injection, and hemoglobin A1c ( HbA1c ) level at baseline were also recorded. Retreatment criteria included persistence of submacular fluid, intraretinal cysts, or CMT of more than 300 μm.Results: Baseline demographics, HbA1c, BCVA, CMT, and TMV values were similar between the vitrectomized and nonvitrectomized groups (p>0.05). The duration between diagnosis of DME and IVR injections was longer in the nonvitrectomized group than in the vitrectomized group (16±5 months vs. 13±4 months, respectively; p=0.045). IVR injection was performed 6.3 times in vitrectomized eyes and 6.1 times in nonvitrectomized eyes during the 24-month period (p>0.05). The mean BCVA improved significantly during the 24-month period in both groups (for vitrectomized group from 0.51±0.26 logMAR to 0.40±0.22 logMAR; for nonvitrectomized group from 0.72±0.28 logMAR to 0.50±0.22 logMAR). The improvement in BCVA was significant at month 6 in nonvitrectomized eyes, while there was no significant improvement in vitrectomized eyes before month 18. Compared to the baseline values, the decrease in both CMT and TMV was significant in months 6, 12, 18, and 24 in the nonvitrectomized group (p<0.05). In the vitrectomized group both CMT and TMV improved significantly only in months 18 and 24 (p<0.05).Conclusion: IVR treatment for DME is equally effective in both vitrectomized and nonvitrectomized eyes. However, the response to treatment is seen later in vitrectomized eyes compared to nonvitrectomized eyes.3