Objective: To describe clinical and serological features of a large series of patients affected by primary Sjogren’s syndrome (pSS), assessing the evolution of the disease in a long-term follow-up study. Methods: Clinical and laboratory data of 250 patients with pSS attending our Unit for a mean follow-up period of 140 months were retrospectively collected and analysed. In all the cases the diagnosis was made according with the recent international criteria. Results: Glandular involvement was almost universally present, typically as the first manifestation of the disease and a slow progression of the salivary and lachrymal dysfunction was seen during the observation period. Extraglandular involvement was mild, quite rare and delayed. The respective percentages for muscle-skeletal disease, urogenital, haematological, skin, pulmonary, gastrointestinal, neurological and renal involvement were 60%, 40%, 24%, 20%, 11%, 7%, 8% and 3%. Only 6 patients developed a lymphoma. The serological pattern of the majority of patients remained constant throughout the follow-up period. Conclusions: pSS is often a benign condition. Since some patients may develop lymphoid malignancies, clinical follow- up is recommended.