We assessed long-term outcomes of autologous microvascular submandibular gland (SMG) transplantation for severe dry eye disease and investigated factors influencing long-term results. From August 1999 to January 2015, 185 patients (200 eyes) with severe dry eye received SMG transplantation. Subjective assessments and ophthalmologic evaluations were performed before and after transplantation. Follow-up results showed successful transplantation in 180 of 200 eyes (success rate: 90%), resulting in marked symptomatic relief of xerophthalmia. Surgery failed due to vascular thrombosis (15 glands) and duct obstruction (5 glands). Follow-up data were available for 163 eyes. Epiphora occurred in 98 (60.1%) eyes and was effectively managed by surgical reduction of graft, topical atropine gel and botulinum toxin injection. Wharton's duct obstruction occurred in 16 (10.6%) eyes and was treated by duct reconstruction. Subjective satisfaction was achieved in 143 (87.7%) eyes. Mean score of fluorescent staining reduced from 11.25 +/- 1.42 to 7.25 +/- 3.37. Postoperative best-corrected visual acuity improved in 85 (56.3%) eyes. Our clinical experience proved that SMG transplantation is effective and grants long-term improvement in severe dry eye. Secretory function of transplanted SMGs remains active and stable. Blood vessel thrombosis, Wharton's duct obstruction, and epiphora are primary factors influencing results.