Purpose: To assess the effects of oral vitamin D supplement therapy on clinical outcomes of intravitreal bevacizumab (IVB) injections in patients with diabetic macular edema (DME). Method: Seventy-one patients with center-involving DME received IVB injections three times monthly. Cases with serum 25-hydroxyvitamin D (25(OH)D) levels <30 ng/ml were divided into treatment and control groups. The treatment group received 50000 IU of oral vitamin D once a week for eight weeks. One month after the third IVB injection, changes in the best-corrected visual acuity (BCVA) and central macular thickness (CMT) were analyzed for each group. Results: Thirty-seven patients had sufficient levels of 25 (OH) D, while 34 patients had insufficient levels. Nineteen cases with deficient levels of 25(OH)D were treated with oral vitamin D, while 15 patients were assigned to the control group. The mean of serum 25(OH)D in patients was 27.9 ng/ml [mean 20.3 ± 5.4 and 17.3 ± 5.4 ng/ml in control and treatment groups, respectively (P = 0.231)]. After three IVB injections, BCVA improved significantly in each group, but the difference between the study groups was not statistically significant. CMT decreased significantly in all the groups. The mean CMT reduction was more prominent in the vitamin D-treated group, but the difference between groups did not reach statistical significance (P = 0.29). Conclusion: In DME patients with vitamin D deficiency, vitamin D supplement therapy had some beneficial effects on CMT reduction following three injections of IVB; nevertheless, these effects were not statistically significant. Definite conclusion needs further prospective studies with a larger sample size.