Purpose To compare clinical outcomes following gel stent implantation via ab externo and ab interno approaches in patients with refractory glaucoma. Patients and Methods This retrospective study included 203 eyes of 185 patients aged ≥45 years who underwent Xen gel stent implantation as a standalone procedure for medically uncontrolled glaucoma (intraocular pressure (IOP) ≥18 mmHg) despite maximum tolerable IOP-lowering medications. One hundred and five eyes underwent gel stent implantation via ab interno approach and 98 via ab externo. Patients with prior conjunctival-incisional glaucoma or cataract surgery were also included. Study parameters were reduction in IOP and number of IOP-lowering medications from baseline to 3, 6, 9 and 12 months postoperatively. Results There were no statistically significant differences in the age, sex, preoperative IOP, number of IOP-lowering medications or cup–disc ratio between the ab interno and ab externo groups at baseline (p > 0.05). At all postoperative time points, mean IOP and percentage reduction from baseline were comparable in both groups (p > 0.05) except at postoperative 6 months when the outcomes were significantly better (p < 0.05) in the ab externo group. The rate of postoperative procedures (5-Fluorouracil injections and bleb needling), the incidence of numerical or clinical hypotony and adverse events were comparable in both groups (p > 0.05). The mean number of IOP-lowering medications was comparable in both groups at all time points. Conclusion The Xen gel stent, whether implanted ab interno or ab externo, is effective in reducing IOP and dependence on topical medications in eyes with refractory glaucoma. The stent may be used in both phakic and pseudophakic patients and is a reasonable option for patients with prior failed trabeculectomy.