OBJECTIVE To study the long-term outcome in patients with Sjögren's syndrome (SS). METHODS We retrospectively studied a cohort of 43 patients with SS; 31 patients with primary SS and 12 patients with secondary SS (6 patients with rheumatoid arthritis, 3 patients with mixed connective tissue disease, 2 patients with systemic lupus erythematosus and 1 patient with systemic sclerosis). Follow-up assessments were performed for 10-20 years following the initial diagnosis. RESULTS During follow-up, 29 patients (67%) with SS developed new extraglandular manifestations including: a small amount of monoclonal gammopathy (10 patients), interstitial pulmonary disease (8 patients), malignancy (4 patients developed cancer, 1 patient developed malignant lymphoma), Raynaud's phenomenon (4 patient), peripheral neuropathy (3 patients), renal disease (2 patients), myopathy (2 patients) and others. Statistically significant differences in the salivary gland scintigraphy existed between the progressed group and the stable group at both the initial diagnosis and ten years later. Patients with anti-Ro (SS-A) antibody had a high incidence of salivary gland enlargement, hypocomplementemia, rheumatoid factor and anti-nuclear antibody. The focus scores of the labial salivary biopsy in anti-La (SS-B) antibody positive patients were significantly higher than in patients without this antibody. No statistically significant differences were noted in symptoms and signs between study entry and follow-up. CONCLUSIONS Although sicca symptoms involving the eyes and the mouth did not progress in most of SS patients, 67.4% of SS patients developed new extraglandular manifestations during the 10-20 years follow-up period.