Purpose To evaluate the efficacy and safety of the Ultrasonic Circular Cyclo Coagulation (UC3) procedure in patients with primary open-angle glaucoma (POAG). Methods Prospective multicenter clinical trial. 42 eyes of 42 patients with POAG, intraocular pressure (IOP) > 21 mmHg, an average of 1.65 failed previous surgeries and an average of 3.2 hypotensive medications were insonified with a probe comprising 6 piezoelectric transducers. 18 patients (group 1) were treated with a 4 seconds exposure time for each shot and 24 patients (group 2) with a 6 seconds exposure time. Follow-up visits were performed at 1 day, 1 week, 1, 2, 3, 6 and 12 months after. Results IOP was significantly reduced in both groups (p<0.05), from a mean preoperative value of 28.6 ± 4.7 mmHg in group 1 and 28.1 ± 8.6 mmHg in group 2 to a mean value of 16.1 ± 2.8 mmHg in group 1 and 16.7 ± 4.4 mmHg in group 2 at last follow-up. Success (IOP reduction >20%) was achieved in 12 of 18 (67%) eyes of the group 1 and in 17 of 24 (71%) eyes of the group 2. Four patients were re-treated. No major intra- or post-operative complications occurred. Conclusion UC3 seems to be an effective and well-tolerated method to reduce intraocular pressure in patients with POAG.