Background: The efficiency and safety of primary open-angle glaucoma with high-frequency deep sclerotomy (HFDS) combined with cataract surgery has to be investigated. Methods: Right after cataract surgery, HFDS was performed ab interno in 205 consecutive patients with open angle glaucoma. HFDS was performed with a custom-made high-frequency disSection 19 G probe (abee tip 0.3 × 1 mm, Oertli Switzerland). The bipolar current with a frequency of 500 kHz is applied. The nasal sclera was penetrated repetitively six times through the trabecular meshwork and consecutively through Schlemm’s canal. Every time, a pocket of 0.3 mm high and 0.6 mm width was created. Results: Mean preoperative intraocular pressure (IOP) was 24.5 ± 2.1 mmHg (range 21 to 48 mmHg). After 48 months, the follow up average IOP was 15.0 ± 1.7 mmHg (range 10 to 20 mmHg). Postoperative IOP has been significantly reduced compared to preoperative IOP for all studied cases (p < 0.001). After 48 months, the target IOP less than 21 mmHg reached in 84.9%. No serious complications were observed during the surgical procedure itself and in the postoperative period. Conclusions: HFDS is a minimally invasive procedure. It is a safe and efficacious surgical technique for lowering IOP combined with cataract surgery.