The clinical presentation and outcome of candidemia has changed in recent years. We compared two 5-year periods (2000–2004 and 2005–2009) in a single institution. We recorded 419 candidemia episodes during the study period (124 in the first period and 295 in the second period). We observed a significant increase in the number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009 (χ² LT <0.001). Candida albicans was the most frequently isolated species (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%). In the second period, episodes were associated with higher comorbidity and were more commonly nosocomial, with a more frequent catheter-related source and an increased rate of C. glabrata infection. No significant differences were observed in susceptibility by species during the study period. According to multivariate analysis, the independent factors associated with higher mortality were shock, age >50 years, elevated comorbidity score (Charlson index >6), and source of candidemia other than catheter. In contrast to the increase in comorbid conditions observed in recent years, mortality remained similar during both periods (37% during the first month). This finding could be attributed to a significant increase in catheter-related candidemia and better outcome, as well as to a potential improvement in the management of antifungal therapy in recent years.