Investigate central retinal thickness (CRT) variability and changes in best-corrected visual acuity (BCVA) after 12 months in patients with retinal vein occlusion (RVO) treated with dexamethasone intravitreal implants. Post hoc analyses of two randomized trials in patients with macular edema associated with branch or central RVO treated with a 0.7-mg dexamethasone implant. Central retinal thickness standard deviation (CRT-SD) and central retinal thickness amplitude (CRT-A) were measures of variability. Analyses included multinomial and simple linear regression. In 400 patients, CRT-SD and CRT-A were significantly associated with central RVO, second dexamethasone implant, and baseline CRT. Baseline BCVA was associated with CRT-A. CRT-SD and CRT-A were significantly correlated with a 12-month change in BCVA (effect sizes of -0.032 and -0.013 letters/µm; P < 0.001). Patients in the highest CRT-SD quartile gained significantly fewer letters (+1.88 letters; 95% CI: -0.46 to 4.23). Greater CRT variability was associated with smaller BCVA improvements in patients with RVO treated with dexamethasone implants. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].