Candida glabrata isolates have reduced in vitro susceptibility to azoles, which raises concerns about the clinical effectiveness of fluconazole for treating bloodstream infection (BSI) by this Candida species. We aimed to evaluate whether the choice of initial antifungal treatment (fluconazole vs. echinocandins or liposomal amphotericin B [L-AmB]-based regimens) has an impact on the outcome of C. glabrata BSI. We analysed data from a prospective, multicentre, population-based surveillance program on candidaemia conducted in 5 metropolitan areas of Spain (May 2010-April 2011). Adult patients with an episode of C. glabrata BSI were included. Main outcomes were 14-day mortality and treatment failure (14-day mortality and/or persistent C. glabrata BSI for ≥48 hours despite antifungal initiation). The impact of using fluconazole as initial antifungal treatment on the patients' prognosis was assessed by logistic regression analysis with addition of a propensity score approach. A total of 94 patients with C. glabrata BSI were identified. Of these, 34 had received fluconazole and 35 had received an echinocandin/L-AmB-based regimen. Patients in the echinocandin/L-AmB group had poorer baseline clinical status. Patients in the fluconazole group were more frequently (55.9% vs 28.6%) and much earlier (median 3 vs 7 days) switched to another antifungal regimen. Overall, 14-day mortality was 13% (9/69) and treatment failure 34.8% (24/69), with no significant differences between the groups. On multivariate analysis, after adjusting for baseline characteristics by propensity score, fluconazole use was not associated with an unfavourable evolution (adjusted OR for 14-day mortality: 1.16, 95% CI 0.22-6.17; adjusted OR for treatment failure: 0.83, 95% CI 0.27-2.61). In conclusion, initial fluconazole treatment was not associated with a poorer outcome compared to echinocandins/L-amB regimens in patients with C. glabrata BSI.