Polymicrobial bloodstream infection (BSI) is an imprecisely defined entity purportedly associated with a worse outcome than monomicrobial BSI. This study examines trends in BSI episodes caused by bacteria and Candida spp. (mixed-BSI) in a large teaching hospital.All episodes of BSI from January 2000 to December 2010 were reviewed. Three groups (n = 54 each) of patients were compared: all adults with mixed-BSI from January 2006 to December 2010 (cases) and randomly selected patients with polybacterial BSI (polyB-BSI) (Control 1) or Candida spp. BSI (Candida-BSI) (Control 2) in this same period.A total of 139 episodes of mixed-BSI were recorded (0.7% of all BSI, 6.9% of all poly-BSI and 18.0% of all Candida-BSI episodes). The incidence of mixed-BSI was 0.21 cases/1000 admissions, increasing from 0.08 (2000) to 0.34 (2010) cases/1000 admissions (P = 0.007). Mixed-BSI represented 11.8% and 22.9% of all episodes of candidaemia in 2000 and 2010, respectively (P = 0.011). Compared with polyB-BSI, mixed-BSI patients showed fewer malignancies, more frequent nosocomial or intravenous catheter BSI source and less frequent intra-abdominal origin, were more frequently admitted to an intensive care unit (ICU), received more antimicrobials and showed a longer hospital stay and higher mortality. Compared with Candida-BSI, mixed-BSI patients showed more severe underlying diseases, were more frequently admitted to an ICU or oncology-haematology unit, showed a higher APACHE II score, more often progressed to septic shock or multiorgan failure and received more antimicrobials. Mortality was similar.Mixed-BSI is a rare, distinct infection with a worse prognosis than polyB-BSI. We were unable to detect differences in the prognosis of mixed-BSI when compared with Candida-BSI.