Abstract Background China has the largest burden of primary angle-closure glaucoma (PACG) worldwide. The mechanism of the angle closure is complex and includes pupillary block and non-pupillary block. Currently, opinion is that laser peripheral iridotomy (LPI) alone is not sufficient to prevent disease progression. Laser peripheral iridoplasty (LPIP) is an alternative and effective way of widening the angle recess in eyes that are affected by primary angle closure (PAC). However, it is not known if greater benefit would be achieved using LPI plus LPIP for PAC with multiple mechanisms (MAC). Thus, the aim of this study is to demonstrate if LPI plus LPIP would be more effective than single LPI in controlling the progression of PAC with multiple mechanisms, based on ultrasound biomicroscopy (UBM) classification. A secondary aim is to determine whether or not this would result in the use of less medication and/or prolong the time to antiglaucoma surgery. Methods This multiple-mechanism angle-closure study will comprise a 3-year, multicenter, randomized, parallel-group, open-label, superiority trial, the aim of which will be to evaluate the safety and efficacy of LPI plus LPIP versus LPI for PAC. It is anticipated that 240 adults, diagnosed with PAC (the mechanism of angle closure will be assessed by UBM and it will be determined whether or not it involves multiple mechanisms) will be recruited from ten ophthalmic centers in China. Participants will be randomly allocated to receive either single LPI or LPI plus LPIP. Participant assessment will be designed to test the rate of disease progression and who will be followed up for 3 years. The primary outcome will be the disease progression rate and a comparison will be made between the LPI and LPI plus LPIP groups using Pearsonâ s Ď 2 test. Logistic regression analysis will be performed to account for the central effect. Discussion If the LPI plus LPIP is found to significantly decrease the rate of PAC progression, this intervention could potentially be a standard therapy to be used to treat PAC when multiple mechanisms are involved in angle closure. Subsequently, this would have the potential to delay the rate of PAC progression to PACG and delay the time to the administration of antiglaucoma medication or trabeculectomy surgery. Trial registration ClinicalTrials.gov, NCT02613013 . Registered on 24 November 2015. In fact, the study was due to start in late October 2015, however, there were no patients recruited in October, and when we registered at ClinicalTrials.gov on 5 November 2015, we received suggestions on the English translation of our protocol from the PRS Team at Clinicaltrial.gov, so the final successful registration date was on 24 November 2015.