Purpose:To evaluate the safety and performance of CO2 laser-assisted sclerectomy surgery (CLASS).Materials and Methods:CLASS using the IOPtiMate system was performed in experimental models and in patients with primary and pseudoexfoliative open-angle glaucoma. CO2 laser was used to achieve deep scleral ablation. Percolation and perforation rates were recorded. Histopathological analysis was performed on laboratory models, complications were recorded and postoperative intraocular pressure (IOP) was measured.Results:Deep scleral ablation and aqueous percolation were repeatedly achieved. Histology disclosed deep scleral craters with a thin intact sclero-corneal tissue at the ablation area with mild, transient and limited thermal damage. Thirty of 37 patients with glaucoma completed 12 months of follow-up. The baseline IOP of 26.3 ± 7.8 mmHg (mean ± SD) dropped to 14.4 ± 3.4 mmHg and 14.3 ± 3.1 mmHg at six and 12 months, respectively (p<0.001). Complications were mild and transitory with no sequelae.Conclusions:CLASS using the IOPtiMate system is a safe and efficacious procedure for achieving effective fluid percolation.