OBJECTIVE To compare outcomes in exfoliation glaucoma versus primary open-angle glaucoma (POAG) after ab interno trabeculectomy alone (Trabectome) or in combination with cataract surgery and intraocular lens (IOL) implantation. METHODS Trabectome Study Group institutions. METHODS Prospective nonrandomized cohort study. METHODS Outcomes included intraocular pressure (IOP), glaucoma medications, complications, secondary procedures, and success, defined as no secondary surgery and IOP less than 21 mm Hg and a greater than 20% reduction from baseline. RESULTS In the ab interno trabeculectomy-alone group, the mean preoperative IOP was 29.0 mm Hg ± 7.5 (SD) in exfoliation glaucoma cases and 25.5 ± 7.9 mm Hg in POAG cases (P<.01). At 1 year, the mean decrease in IOP was -12.3 ± 8.0 mm Hg and -7.5 ± 7.4 mm Hg, respectively (P<.01); the secondary procedure rate was 20.9% and 34.9%, respectively (P=.02); and the cumulative probability of success was 79.1% and 62.9%, respectively (P=.004). In the combined ab interno trabeculectomy-IOL group, the mean preoperative IOP was 21.7 ± 8.4 in exfoliation glaucoma cases and 19.9 ± 5.4 mm Hg in POAG cases (P=.06). At 1 year, the mean decrease in IOP was -7.2 ± 7.7 and -4.1 ± 4.6, respectively (P<.01); the secondary procedure rate was 6.7% and 6.1%, respectively (P=.88); and the cumulative probability of success was 86.7% and 91.0% (P=.73), respectively. CONCLUSIONS Ab interno trabeculectomy using this new incisional procedure safely lowered IOP to the mid teens, with an overall greater reduction in exfoliation glaucoma and improved success when combined with cataract surgery.