Background/Objectives: To investigate if the visual and anatomic response to the first dexamethasone implant (DEX) predicts the 12-month clinical outcome after shifting to fluocinolone acetonide (FAc) implant in patients with diabetic macular oedema (DMO). Methods: Retrospective cohort study including pseudophakic patients with previously treated DMO, undergone one or more DEX injections before FAc. Functional and morphologic response to DEX was defined based on the best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after the first DEX, respectively. Steroid-response was defined as intraocular pressure (IOP) elevation ≥5 mmHg or IOP > 21 mmHg after any previous DEX exposure. Pairwise comparisons for BCVA, CMT, and IOP after FAc were performed with linear mixed models and a repeated-measure design. Results: Forty-four eyes of 33 patients were included. Patients were shifted to FAc after a mean ± standard deviation of 4.6 ± 3.2 DEX injections. Overall, BCVA and CMT improved during the first 12 months after switching to FAc (p = 0.04 and p < 0.001, respectively). Only eyes with a good morphologic response to DEX had a significant CMT reduction after FAc (p < 0.001), while no significant relationship was found between BCVA improvement after DEX and after FAc. IOP elevation occurred in 9 eyes (20%) following DEX implant. These eyes carried a 20-fold increased risk of having an IOP rise after FAc (p < 0.001), with a non-linear relationship between the IOP increase after DEX and the one after FAc. Conclusion: The response to previous DEX may anticipate the morphologic response to subsequent FAc. Eyes with steroid-induced IOP elevation after DEX are at a high risk of IOP increase after FAc. The visual response after FAc was not associated with the visual response to previous steroids, indicating that FAc may have a role also in patients refractory to DEX implant.