Purpose: To evaluate the efficacy of CO2 laser-assisted sclerectomy surgery (CLASS) compared with classic nonpenetrating deep sclerectomy (NPDS) with implant in medically uncontrolled glaucoma patients. Materials and Methods: Patients who underwent primary filtration surgery with CO2 laser system at the time interval between July 2010 and April 2011 were identified, their medical files were reviewed, and their results were compared with matched control group who underwent classic NPDS with intrascleral implant at the same time period. Intraocular pressure (IOP) was measured at baseline, 1 week, and 3, 6, 12, 18, and 24 months, respectively. Main outcome measures were: IOP, use of supplemental medical therapy, and failure (5 mm Hg > IOP > 18 mm Hg, reoperation for glaucoma, or loss of light perception). Results: A total of 58 patients were reviewed, including 27 in the CLASS group and 31 in the NPDS group. For the CLASS group the follow-up (mean +/- SD) was 20.7 +/- 6.8 months, the mean preoperative IOP was 23.3 +/- 8.2 mm Hg (range, 10 to 38 mm Hg), and the mean number of antiglaucoma medication before surgery was 3.0 +/- 1.0 (range, 1 to 4). At final follow-up visits, the mean IOP was 11.7 +/- 3.1 mm Hg (range, 6 to 19 mm Hg), and the mean number of antiglaucoma medication was reduced to 1.0 +/- 1.6 (P < 0.0003). The complete success rate (IOP <= 18mm Hg without antiglaucoma medication) was 73% and the qualified success rate (IOP <= 18 mm Hg with/without antiglaucoma medication) was 96%. For the control group the mean follow-up was 17.6 +/- 6.7 months, the mean preoperative IOP was 23.1 +/- 7.3mm Hg (range, 14 to 44 mm Hg), and the mean number of antiglaucoma medication before surgery was 3.0 +/- 0.8 (range, 1 to 4). At final follow-up visits, the IOP was 13.3 +/- 3.6mm Hg (range, 8 to 20 mm Hg), and the mean number of antiglaucoma medication was reduced to 0.7 +/- 1.1 (P < 0.0004). The complete success rate and the qualified success rate were 71% and 89%, respectively. Conclusions: A new technique using a CO2-laser ablation system allows precise and easy creation of the scleral space and ablation of Schlemm canal. This technique has been shown to be as efficient as the standard NPDS surgery in terms of IOP-lowering effect. This would render the deep sclerectomy an easier glaucoma surgery.