To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) as a replacement for medical therapy in primary open-angle glaucoma (POAG). A prospective, randomized, controlled study.SLT treatment with SOLO SLT Nd: YAG laser was provided to 45 participants with advanced POAG (67 eyes, IOP ≤ 21 mmHg, 1 mmHg = 0.133 kPa) under anti-glaucomatous medications control). A table of random numbers was created by simple randomization method. Participants were randomly divided into two groups: the standard-energy group (34 eyes), which received a 270° standard-energy SLT treatment and the sub-threshold energy group (33 eyes), which received a 360° sub-threshold energy treatment. The intraocular pressure (IOP) before and after SLT, daytime IOP curve, dosage of anti-glaucoma drugs and treatment complications were observed, which were be followed up for 6-9 months (average 6.4 months). Two-tailed t-test or paired t test was used when the continuous variables were normal distribution, such as the basic data, daily fluctuations of IOP, laser energy. Non-parametric Mann-Whitney U test or Wilcoxon rank test was used when data was not distributed normally, such as drug category. Chi-square or Fisher's exact test was used when count variables such as success rate and complications were analyzed. The number of anti-glaucomatous drugs used in the standard-energy group and the sub-threshold energy group before SLT was (2.3 ± 0.5) and (2.1 ± 0.4), respectively; whereas, after the last treatment, it reduced to (1.3 ± 0.5) and (1.1 ± 0.3), respectively (Z = -5.477, -5.396; P < 0.05). The success rate of the standard-energy group and the sub-threshold energy group was 91.1%, and 87.9%, respectively, which was not significant different (P = 0.70). Laser treatment was found to reduce the IOP fluctuation during the daytime.IOP fluctuation decreased from (3.6 ± 1.0) mmHg to (2.3 ± 1.0) mmHg in the standard-energy group, and decreased from (3.9 ± 1.4) mmHg to (2.4 ± 0.9) mmHg in the sub-threshold energy group, which was significant different (t = 4.911, 4.679; P < 0.05). The total laser energy of the standard-energy group (47.8 ± 6.0) mJ was higher than the sub-threshold energy group (43.2 ± 5.1) mJ (t = 12.006, 3.233; P < 0.05). However, there was no significant difference in the daily IOP fluctuations, success rate, reduction of medication categories, preoperative and postoperative IOP, and adverse reactions between the two groups. SLT is a safe and effective replacement for medical therapy in primary open-angle glaucoma treatment. SLT could reduce the applications of anti-glaucoma drugs. There was no significant difference between therapeutic effects of which eyes received 360° sub-threshold energy and 270° standard-energy.