BACKGROUND: Glaucoma is a major cause of sight-loss worldwide, with the highest regional prevalence and incidence reported from Africa. The most common low-cost treatment used in this region to control glaucoma is long-term timolol eye drops. However, side effects, low adherence, limited availability, and high long-term costs are a challenge. Selective laser trabeculoplasty (SLT) is a short outpatient procedure to lower eye pressure but was not formally compared with standard treatment in Africa. We tested the hypothesis that SLT is superior to timolol 0·5% eye drops for the treatment of open-angle glaucoma. METHODOLOGY: A randomised, controlled, parallel group, single-masked clinical trial was conducted at KCMC Eye Department, Moshi, Tanzania. Participants (aged ≥18 years) had open-angle glaucoma, intraocular pressure (IOP) >21mmHg and neither previous glaucoma surgery nor asthma. They were randomly allocated to receive timolol 0.5% eye drops twice daily or SLT. The primary outcome was the proportion of success after one year defined as an IOP ≤18mmHg for eyes with advanced glaucoma (disc damage likelihood scale (DDLS) 8-10) and IOP ≤21mmHg for moderate glaucoma (DDLS 5-7). Re-explaining the application of eye drops or a repeat SLT was permitted once. Further outcomes included safety, acceptance, vision-related quality of life (VRQoL) using the WHO/PBD VF20 questionnaire, preservation of visual acuity, and cost. Results were analysed by intention to treat using logistic regression; generalised estimating equations were used to adjust for the correlation between eyes. RESULTS: 201 participants (382 eligible eyes) were enrolled; 100 people (191 eyes) were randomly assigned to timolol and 101 (191 eyes) to SLT. At baseline, mean IOP was 26.7mmHg (SD 6.9mmHg), 162 eyes had moderate glaucoma and 220 eyes advanced glaucoma. DDLS yielded an area under the receiver operating characteristics curve (AROC) of 0.90 (95% CI 0.87-0.93), compared to AROC for vertical CDR of 0.88 (95% CI 0.85-0.91), p=0.048, for identifying severe/end-stage disease. After one year, 339 eyes were analysed (89%). Treatment was successful in 55/176 eyes (31.3%) in the timolol arm (39 eyes without repeat counselling) and in 99/163 eyes (60.7%) in the SLT arm (66 eyes without repeat SLT); odds ratio 3.37 (95% CI 1.96-5.80, p<0.0001). The multivariable analysis identified baseline IOP <25mmHg, moderate glaucoma and no exfoliation material as predictors of success. Safety, acceptance, VRQoL, preservation of vision after one year were similar in both groups. Depending on the number of eyes treated annually, SLT can be an affordable and cost-covering intervention. A post hoc analysis of the SLT group showed a response (IOP reduction of 2mmHg or more) in 81% of eyes after SLT and 19% had no response after primary SLT. Among non-responders, 70% responded and 30% showed no response after repeat SLT (p=0.872). SLT treatment response was correlated between eyes: primary SLT in 85 pairs, chi-squared=18.07 (p<0.001), after repeat SLT in 47 pairs 3.68 (p=0.055). The most parsimonious model of absolute IOP reduction after primary SLT included age <70 years, no timolol eye drops before enrolment, IOP ≥25mmHg and a minimum height of the trabecular meshwork of >1/2 of the laser spot size as predictors, and only IOP ≥25mmHg for the model after repeat SLT. CONCLUSIONS: SLT was superior to timolol for managing open-angle glaucoma in this East African setting. It has potential to transform the management of glaucoma in Africa, even where the prevalence of advanced stages of this blinding disease is high.