To assess macular thickness fluctuations and their association with visual acuity outcomes in eyes with diabetic macular edema treated with an intravitreal dexamethasone (DEX) implant. The SD of all postbaseline central subfield thicknesses (CST) recorded over a 12-month period after the first injection of the DEX implant was used to quantify CST fluctuations. Linear regression models were used to identify factors associated with the visual acuity at 12 months (measured with the Early Treatment of Diabetic Retinopathy Study score) and predictors of CST SD. A retrospective review of 80 eyes of 80 patients treated with the DEX implant for diabetic macular edema revealed a CST SD of 75.3 ± 50.3 µ m. The CST SD was negatively associated with the visual acuity at 12 months (-7.7 Early Treatment of Diabetic Retinopathy Study letters for each 100- µ m increase in CST SD, P = 0.01), while changes in CST from baseline did not show any significant association. Eyes were stratified into quartiles based on the CST SD, and a difference by -14.2 letters in visual acuity at 12 months was observed between the first and fourth quartiles ( P <0.001). Significant predictors of CST SD included the baseline visual acuity (-12.0 µ m for each 10-letter increase, P = 0.02) and the number of DEX injections received (n = 17.1, P = 0.03). Greater fluctuations in retinal thickness were found to be associated with poorer visual outcomes in eyes with diabetic macular edema treated with the DEX implant. Analyzing the CST SD could be a more predictive indicator of visual prognosis than individual measurements of the CST.