We prospectively analysed the microbiological isolates of all febrile/infectious episodes occurring at our haematology unit during 2 consecutive 18-month periods. Microbiologically documented infections (MDI) and antibiotic resistance were correlated with type and status of haematological disease, neutropenia, levofloxacin prophylaxis, central venous catheter and clinical outcome. Three hundred and ten MDI were observed and 369 pathogens were isolated. Gram-negative bacteria represented 49.3% and Gram-positive bacteria 40.9% of all pathogens. Fungal infections represented only 8.9% of MDI. A significant decrease in Staphylococcus aureus (p < 0.001) and an increase in enterococci, viridans streptococci and Pseudomonas spp. (p = 0.004) were observed during the second period. Four multiresistant (Multi-R) Pseudomonas were isolated, all during the last 12 months. The death rate in MDI was 8.7%, bacteria accounting for 70.4% of them. Enterococci, streptococci and Pseudomonas spp. infections were involved in 44.4% of MDI with an unfavourable outcome. Multi-R pathogens were involved in 4 cases (3 vancomycin-resistant enterococci and 1 Multi-R Pseudomonas), their death rate being 25%. Multivariate analysis showed that an infection due to a mycotic or a Multi-R pathogen was associated with an unfavourable outcome. The recent emergence of enterococci, viridans streptococci and Pseudomonas spp., particularly if Multi-R, is a major concern in haematological patients.