AIM: To evaluate the safety and efficacy of lacrimal canalicular plug in the treatment of severe chronic ocular graft-versus-host disease(coGVHD).METHODS: Retrospective study. A total of 9 patients with severe coGVHD admitted to the dry eye clinic of the Affiliated Hospital of Xuzhou Medical University from June to September 2022 were included. All patients underwent binocular inferior lacrimal canaliculus plug. Ocular surface disease index(OSDI)score, tear meniscus height(TMH), corneal fluorescein staining(CFS)scores, conjunctival lisamine green staining(CLGS)score, noninvasive breakup time(NIBUT), Schirmer Ⅰ test(SⅠt)and the infiltration of Langerhans cells in the superficial corneal stroma tested by confocal corneal microscopy were observed before treatment and at 1 and 3 mo after treatment. At the same time, the complications related to lacrimal canalicular plug implantation were evaluated.RESULTS: The OSDI score decreased from 67.33±12.64 before treatment to 21.89±6.07 after 3mo of treatment(P<0.01); TMH increased from 0.09±0.02mm to 0.21±0.03mm after 3mo of treatment(P<0.05), and NIBUT increased from 2.24±0.68s before treatment to 6.77±2.05s after 3mo of treatment(P<0.01). In addition, the CFS and CLGS also changed significantly, from 9.11±1.45 and 6.33±1.00 before treatment to 2.22±0.67 and 2.56±0.88 at 3mo after treatment, respectively(all P<0.01). The density of Langerhans cells decreased from 140.22±38.18cells/mm2 before treatment to 39.67±9.75cells/mm2 3mo after treatment(P<0.01). SⅠt showed no significant difference before and after treatment(F=0.059, P=0.943). During the whole follow-up period, no complications such as plug abscission were observed.CONCLUSION: Lacrimal canalicular plug is safe and effective in the treatment of severe coGVHD. It can significantly improve the symptoms and signs of dry eye patients and reduce inflammatory reaction.