Objectives: The aim of this study was to examine the differences in clinical manifestations and comorbidities in men and women with Sjögren’s syndrome treated in the University Hospital of Split in the period from 2010 to 2020. Methods: The study included 317 patients with a confirmed diagnosis of SS in the period from 2010 to 2020. The data was collected from outpatient clinics, stationers and daily hospital of the Department of Rheumatology and Clinical Immunology of the Clinic for Internal Diseases of University Hospital of Split. From the insight of the protocol and archive of the history of the disease, we have collected demographic characteristics (age, sex) and accompanying clinical manifestations and comorbidities. During the collection process, the data was entered into Microsoft Excel program. The SPSS 20 for Windows package (IBM, New York, USA), χ2 test, Fisher test, Fisher-Freeman-Halton test, univariate logistic regression, Firth univariate logistic regression and multivariate logistic regression were used in the statistical analysis. Results: Out of a total of 317 patients with SS, there were 17 (5.4 %) men and 300 (94.6 %) women. The median age of the patients was 64 years (min-max: 19-89 years, Q1- Q3: 54-72 years). We have obtained a statistically significantly higher chance of developing lung diseases, vasculitis and lymphoma in men, and a statistically significantly higher chance of developing hypothyroidism in women. According to the median age, the patients were divided into 3 groups: <59 years, 59 - 69 years, > 69 years. Using Fisher-Freeman- Halton test we have proved a statistically significant association of the younger age group with thrombocytopenia and APS. In elderly patients, statistically significant results were related to cardiovascular diseases, hypertension, osteoporosis, diabetes, dyslipidemia, RA, SSc, and sSS. In multivariate logistic regression in which age and sex were taken as independent variables, we have confirmed the association of the primary SS with the male sex and the younger age group. The incidence of pSS in men was 8.7 times higher than in women (P = 0.038), while the incidence of primary SS in the group of patients <59 years was 2.1 times higher compared to the group of patients 59 - 69 years (P = 0.013). Conclusion: Our study showed that men with Sjögren's disease had a higher incidence of lymphoma, vasculitis and lung involvement, while women had a higher incidence of hypothyroidism. Furthermore, thrombocytopenia and APS were more common in younger patients. In contrast, cardiovascular diseases, hypertension, diabetes, dyslipidemia, osteoporosis, rheumatoid arthritis, systemic sclerosis and secondary SS were characteristically more common in elderly patients. Despite the fact that men are less likely to develop pSS, our research shows that at the time of diagnosis, male patients have a more serious form of the disease than women. This suggests that the pathogenic mechanisms of pSS may differ in women and men and that the health care of these patients should take into account these specificities. Nevertheless, for precise conclusions on this issue, it is necessary to include wider population and monitor it over a longer time period.