Purpose: To compare outcomes between 2 nonvalved glaucoma drainage devices (GDDs) used to treat refractory glaucoma or in patients with neovascular/uveitic glaucoma likely to be poorly responsive to less aggressive therapies. Design: Retrospective, nonrandomized, multicenter comparative study. Participants: A total of 117 eyes from 117 patients. Methods: Retrospective chart review of patients who underwent implantation of the Baerveldt (BGI) (Abbott Medical Optics, Abbott Park, IL) or the Molteno3 glaucoma implant (MGI) (Molteno Ophthalmic Limited, Dunedin, New Zealand). Noninferiority of the MGI versus the BGI was tested with Cox and mixed-effects regression models. Interventions in each group were analyzed with chi-square tests. Main Outcome Measures: The primary outcome was time until device failure, defined as intraocular pressure (IOP) >21 mmHg or a reduction <20%, hypotony, reoperation for glaucoma, or loss of light perception. Secondary outcomes were intraoperative time, postoperative IOP, number of IOP-lowering medications, and visual acuity (VA). Results: The MGI could not be deemed noninferior to the BGI with regard to time until device failure (hazard ratio [HR], 0.83; confidence interval [CI], 0.41–1.65). The MGI was noninferior to the BGI when comparing postoperative IOP, a difference of −0.40 mmHg (95% CI, −1.74–0.93). The MGI needed 2% fewer medications (ratio of 0.98, 95% CI, 0.79–1.22), but noninferiority could not be claimed. With regard to VA, the MGI's mean was 0.10 logarithm of the minimum angle of resolution (logMAR) higher (95% CI, −0.01–0.21), but noninferiority testing was again inconclusive. Intraoperative time for the MGI was 15.7 minutes shorter versus the 350 mm2 plate size BGI (P < 0.001) and 4.3 minutes shorter versus the 250 mm2 plate size BGI (P = 0.32). More patients in the MGI group needed secondary operative management (11%, P = 0.03). Conclusions: The MGI was noninferior to the BGI in lowering IOP. Differences in time until device failure, VA outcomes, and medication use were inconclusive. The MGI required more secondary operative interventions. The MGI required less time to implant than the BGI's 350 mm2 plate size implant. Overall, the use of both GDDs is justifiable to lower IOP when more conservative management has failed.