Purpose <p>Cataract and glaucoma, often coexist and present a surgical challenge requiring optimal visual and IOP outcomes. This study compared the clinical outcomes of phaco-trabeculectomy (PHACO-Trab) and manual small incision cataract surgery with trabeculectomy (MSICS-Trab) in patients with coexisting cataract and primary open-angle glaucoma.</p> Methods <p>This prospective, randomized, interventional single-masked clinical trial enrolled 200 eyes from 122 patients with coexisting cataract and primary open-angle glaucoma. Patients were assigned to undergo either phacoemulsification with trabeculectomy (PHACO-Trab) or manual small incision cataract surgery with trabeculectomy (MSICS-Trab). At 24 weeks, 151 eyes from 92 patients completed follow-up and were analyzed (PHACO-Trab, <i>n</i> = 77; MSICS-Trab, <i>n</i> = 74). The primary outcome was change in intraocular pressure (IOP), while secondary outcomes included best-corrected visual acuity (BCVA), postoperative complications, and reduction in antiglaucoma medications, assessed up to 24 weeks. Data was analyzed using SPSS v22; independent t-tests and chi-square tests compared continuous and categorical variables, respectively, while multivariate logistic regression identified predictors of surgical failure. Statistical significance was defined as <i>p</i> &lt; 0.05.</p> Results <p>Both PHACO-Trab and MSICS-Trab significantly improved BCVA and reduced IOP at 24 weeks. Mean BCVA was 0.414 logMAR (PHACO-Trab) vs. 0.523 logMAR (MSICS-Trab) (<i>p</i> = 0.187), and mean IOP dropped to 15.31 ± 6.28 mmHg and 14.38 ± 3.24 mmHg, respectively (<i>p</i> = 0.204). Complete surgical success was similar: 71.4% (PHACO-Trab) vs. 70.3% (MSICS-Trab) (<i>p</i> = 0.939). MSICS-Trab had significantly higher rates of hypotony (<i>p</i> = 0.043), posterior capsule opacification (<i>p</i> = 0.047), and surgically induced astigmatism (<i>p</i> &lt; 0.0001). Refractive outcomes were more favorable in PHACO-Trab, with more eyes achieving target refraction (<i>p</i> = 0.021). Both groups showed significant reductions in the proportion of participants on antiglaucoma medications at endpoint. Independent predictors of surgical failure at 24 weeks were baseline IOP ≥ 21 mmHg (AOR 10.54, 95% CI 2.45–45.37; <i>p</i> = 0.002), worse visual field mean deviation (AOR 5.68, 95% CI 1.93–16.71; <i>p</i> = 0.002), and the presence of postoperative complications (AOR 2.59, 95% CI 1.11–6.08; <i>p</i> = 0.028).</p> Conclusions <p>Both phaco-trabeculectomy and MSICS-trabeculectomy improved visual and IOP outcomes in patients with coexisting cataract and glaucoma. PHACO-Trab showed better refractive results and fewer complications, while MSICS-Trab remains a cost-effective alternative. Within the limits of the sample size and 24-week follow-up, outcomes appeared broadly comparable. Surgical choice should consider patient profile, surgeon expertise, and resource availability. Larger multicenter studies with longer follow-up are needed to confirm these findings.</p> Trial registration number <p>NCT06739343.</p> Registration date <p>December 18, 2024 4:27 PM.</p>