To investigate the epidemiology of systemic sclerosis (SSc) in southern Europe, we assessed the incidence, prevalence, clinical spectrum, and survival of patients diagnosed with SSc in the Lugo region of northwestern Spain. Between January 1988 and December 2006, SSc was diagnosed in 78 Lugo residents according to the criteria proposed by LeRoy and Medsger and/or the 1980 American College of Rheumatology (ACR) preliminary criteria for the classification of SSc. However, only 44 (56.4%) of the 78 patients fulfilled the 1980 ACR criteria for the classification of SSc. The mean age at the time of disease diagnosis was 59.8 +/- 13.3 years. Twenty-three (29.5%) met definitions for diffuse SSc (dSSc), and 55 (70.5%) for limited SSc (lSSc). Patients with lSSc had a longer disease duration before the diagnosis (10.2 +/- 12.0 yr) than those with dSSc (3.7 +/- 3.2yr) (p < 0.001). Based on the criteria proposed by LeRoy and Medsger and/or the 1980 ACR criteria for the classification of SSc, the overall age- and sex-adjusted annual incidence rate over the 19-year study period was 2.3 (95% confidence interval [CI], 1.6-2.5) per 100,000 population aged 15 yr and older (women: 3.5 [95% CI, 2.3-3.9]; men: 1.0 [95% CI, 0.5-1.4]; p < 0.001). Using only the 1980 ACR criteria for SSc, the total annual-adjusted incidence rate was 1.2 (95% CI, 0.9-1.6) per 100,000 population aged 15 years and older (women: 1.8 [95% CI, 1.2-2.5]; men: 0.7 [95% CI, 0.3-1.2]; p < 0.001). The incidence increased significantly in individuals aged 45 years or older. The overall incidence rates of SSc increased over the length of the study (p for trend in the total incidence < 0.001). This was mainly due to a progressive increase of SSc in women between 1993 and 2002. By December 31, 2006, the overall age-adjusted SSc prevalence in the Lugo region of patients who met the criteria proposed by LeRoy and Medsger and/or the 1980 ACR criteria was 27.7 (95% CI, 21.1-35.84) per 100,000 population aged 15 years and older. Cardiopulmonary complications were the leading cause of death (13 of 20 cases). Compared with that in the general population, the probability of survival in patients with SSc was significantly reduced (p < 0.001).The current study establishes a baseline estimate of the incidence and clinical spectrum of SSc in northwestern Spain. According to our results, the incidence and prevalence of SSc in northwestern Spain are similar to those found in Greece and some regions of the United States. Our data confirm a reduced probability of survival in patients with SSc.