Febrile neutropenia is associated with significant morbidity and mortality. Managing infectious in neutropenic patients remains a dynamic process, making necessary timely and efficient empirical antibiotic therapy. The implementation of critical pathways has been suggested as a strategy to improve clinical effectiveness. This study evaluated the compliance with an institutional critical pathway for the management of febrile neutropenia and the impact on clinical outcomes at Hospital de Clínicas de Porto Alegre, Brazil (HCPA). We performed a cohort study that prospectively included patients hospitalized from January 2004 to December 2005 and presented febrile neutropenia (190 episodes). Historical controls were selected from March 2001 to April 2003 (193 episodes) before the critical pathway was introduced. This study showed a low rate of full compliance (21.6%; 95% CI 15.7-27.5) with the critical pathway. In most cases, there was partial compliance (67.9%; 95% CI 61.3-74.5). Despite the moderate adherence observed, we recorded a decrease in in-hospital all-cause mortality in the sample studied after protocol implementation (from 24.4 to 14.4%; P = 0.017) and reduction in the length of use of cephalosporin and quinolones. In conclusion, implementation of a critical pathway seems to be an effective strategy to improve clinical outcomes in patients hospitalized with febrile neutropenia.