<i>Aim:</i> This is a pilot study of 10 eyes of 6 patients. This paper describes the preparation and clinical evaluation of succinylated collagen punctal plugs (SCPP) in the treatment of dry eye syndrome (DES). <i>Methods:</i> SCPP were prepared from succinylated collagen with the exact dimensions of the punctum (length 1.5–2.5 mm, diameter 0.2–0.5 mm, water content between 50 and 55%). All the patients were clinically evaluated for best corrected visual acuity (BCVA), tear fluid levels (TFL), protein content, tear fluid osmolarity (TFO), fluorescence staining of the cornea and tear break-up time (TBUT) before and after punctal occlusion with SCPP. <i>Results:</i> TFL improved among all the patients after punctal occlusion with SCPP. BCVA showed improvement in case 4 (right eye/left eye), case 5 (left eye) and case 6 (right eye), who had developed dry eyes due to environmental conditions. Protein content increased on day 7 in all the patients and gradually decreased. TFO decreased on days 3 and 5 in all patients after punctal occlusion with SCPP, and showed the same levels on day 14. TFL, PC, TFO and TBUT showed significant improvement in all the patients after punctal occlusion with SCPP. <i>Conclusion:</i> All patients experienced symptomatic relief after punctal occlusion with SCPP. There was no discomfort, foreign body sensation, plug extrusion, corneal aberration, infection, or formation of pyogenic granuloma with SCPP. SCPP stands as a promising alternative to other punctal plugs in the treatment of DES.