Background Cigarette smoking has been found to play a pathogenic role in several autoimmune diseases. However, data about its influence on Sjögren's syndrome (SS) is scarce [1,2].Objectives To assess the impact of cigarette smoking on patients with SS.Methods This was a cross-sectional study in which consecutive patients with SS (2002 AECG) followed at a single center were included. Smoking status (ever) together with additional environmental factors and clinical and laboratory characteristics were assessed. Bivariate analysis and the mixed-cluster methodology based on multivariate descriptive methods were employed to analyze data.Results Out of a total of 277 patients, 94% were women. The mean age of patients was 51.2 ± 12.5 years, and the mean duration of the disease was 7.1 ± 7.1 years. By Chisholm and Mason classification, 93% of patients were positive for a minor salivary gland biopsy. Anti-Ro and anti-La antibodies were present in 65% and 40% respectively (by ELISA). Polyautoimmunity was registered in 43% of patients. Smokers showed a longer duration of the disease and were mostly men. Cigarette smoking was associated with parotidomegaly (OR: 1.9; 95%CI 1.05–4.3; p=0.03), polyautoimmunity (OR: 1.9; 95%CI 1.2–3.3; p=0.009), acid peptic disease (OR: 2.3; 95%CI 1.4–4.0; p=0,0008), and coffee consumption (OR: 1.7; 95%CI 0.98–3.6; p=0.04). In order to clarify whether the observed associations were influenced by gender or coffee consumption, 4 clusters were built: 1) men with a high frequency of smoking and coffee consumption (5.6%), 2) women who exclusively reported coffee consumption (42%), 3) women who all drank coffee and smoked cigarettes (30%) and 4) women with no coffee consumption but a third had been exposed to tobacco (22.4%). Cluster 2 patients were statistically less prone to present factors found in the bivariate analysis suggesting that coffee consumption may counteract the harmful effects of smoking.