Objectives: To evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, post- operative intraocular pressure (IOP) and intracameral bleeding were analyzed in 25 diabetic and 84 non-diabetic patients with primary open angle glaucoma (POAG) or ocular hypertension (OH). Results: The mean follow-up period for all 109 eyes was 35.3±24.8 months. There was no significant difference in pre-operative IOP between diabetic and non-diabetic cohorts. However, the post-surgical IOP between 3 months and 2 years was significantly higher in the diabetic cohort (P=0.019 to 0.001). The 3-year survival probability of achieving an IOP≦15 mmHg was 17.8±0.09% in diabetic patients, significantly lower than the 30.4±0.06% observed in non- diabetic patients (P=0.042 Log-rank test). The 3-year survival probability of achieving an IOP≦18 mmHg was 56.7±0.12% in diabetic patients compared to 79.5±0.05% in non-diabetic patients, indicating a marginally significant difference between diabetic and non-diabetic cohorts (P=0.065). When the random effect of diabetes mellitus (DM) was analyzed alongside the fixed effects of preoperative IOP, age, refractive error and extent of canal opening using a multivariate linear mixed model, DM emerged as a significant risk factor for higher postoperative IOP at both 6 and 12 months (P<0.001). Conclusions: Diabetes mellitus is a significant risk factor for poor outcomes following Schlemm’s canal based MIGS, particularly in achieving lower postoperative IOP.