Purpose To compare early-stage intrableb structural changes after Ex-PRESS surgery using anterior-segment optical coherence tomography between primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG). Methods Twenty-five POAG eyes and 15 XFG eyes that underwent Ex-PRESS surgery were evaluated. Intrableb images were classified into four categories based on previously reported scattering intensity: high-, medium-, and low-scattering walls and fluid-filled spaces. Bleb measurements were evaluated in both groups throughout 6 postoperative months. The 3-year surgical success was defined by the criteria intraocular pressure (IOP) < 18 mmHg and IOP < 15 mmHg with or without medications. Results The fluid-filled space volume at 3 and 6 months ( P = 0.005 and P = 0.022, respectively) and the volume ratio of the low-scattering wall to the bleb wall ( P = 0.028) at 6 months were significantly smaller in XFG than POAG postoperatively. The volume ratio of the high-scattering wall to the bleb wall was correlated positively ( P = 0.007) with the IOP, and that of the low-scattering wall to the bleb wall was correlated negatively ( P = 0.002) with the IOP in XFG. The 3-year surgical success rates for both criteria were significantly lower in XFG than POAG. Conclusions Fluid-filled spaces were smaller in XFG than in POAG after Ex-PRESS surgery. The proportion of the high-scattering wall tended to increase and the low-scattering wall tended to decrease in XFG eyes with high IOP. Early-stage intrableb structural changes differed between POAG and XFG and may affect the prognosis. Translational Relevance Our cutting-edge observation of intrableb fibrosis can be an important predictor of the surgical outcome.