PURPOSE: To determine the comparative effectiveness of generic latanoprost (GL) to its branded (BL) counterpart and other brand-name prostaglandin analogs(bPGAs) in preventing the need for additional therapy in the treatment of primary open angle glaucoma(POAG). METHODS: Retrospective cohort study using U.S. commercial medical claims data. All new POAG patients from 2000–2015 who initiated treatment with either GL or BL were included. Exclusion occurred for having less than 2 years of time in the plan prior to diagnosis, previous use of glaucoma medications or any diagnosis of glaucoma other than POAG at any time. Analyses compared GL to BL and also to those who received any branded PGA after 2011 (when the generic became available). Cox proportional hazard regression was used to assess the hazards of filling a prescription for a second IOP-lowering medication or having surgical intervention, individually and either outcome combined. RESULTS: 6,317 and 4,150 POAG patients were treated with GL and BL, respectively. After 2010, 6,317 GL and 3,703 bPGA POAG patients met criteria for inclusion. After adjustment, compared to BL, the GL conferred a reduced hazard of having a glaucoma procedure performed (HR=0.72, 95%CI:0.62–0.84, p<0.001) and the combined outcome(HR=0.90, 95%CI:0.83–0.97, p=0.006), but was not associated with having a second IOP medication(HR=0.95, 95%CI:0.87–1.03, p=0.18). Compared to the bPGAs, however, GL conferred a reduced hazard in each comparison(2(nd) IOP medication HR=0.87,95%CI:0.81–0.94, p<0.001; surgery HR=0.70,95%CI:0.61–0.81, p<0.001; combined HR=0.85,95%CI:0.79–0.92, p<0.001). Sensitivity analyses confirmed these findings. CONCLUSIONS: Generic latanoprost was no less and possibly more effective in preventing the need for additional intervention than branded PGAs.