The use of punctal plugs in the treatment of keratoconjunctivitis sicca (KCS) in inflammatory eye disease remains controversial because of the potentially increased retention time of tears enriched with inflammatory cytokines that may aggravate eye inflammation. We describe the safety and efficacy of punctal occlusion in a retrospective analysis of 19 patients (16 men) with KCS due to chronic GvHD (cGvHD). Efficacy and safety were assessed by subjective and objective criteria (symptoms, corneal fluorescein staining, tear film break-up time (BUT), Schirmer I test, Jones test and visual acuity). Follow-up was from plug insertion until maximum one year after punctal occlusion. After punctal occlusion, patients reported a significant increase in subjective comfort (1.10 vs 0.59 on a scale ranging from no symptoms (0) to severe impairment (2), Po0.001). Pathological corneal fluorescein staining decreased significantly (Po0.001) and tear film BUT remained unchanged (5.98 vs 4.0 s, P ¼ 0.79). Measurement of tear secretion or retention time showed a non-significant trend for improvement in the Schirmer I (3.0 vs 3.40 mm, P ¼ 0.08) and Jones (1.36 vs 2.8 mm, P ¼ 0.08) tests. The logMAR visual acuity remained unchanged. Punctal occlusion achieved a significant improvement in subjective symptoms and objective findings in ocular GvHD without increasing ocular inflammation.