OBJECTIVE: To compare the effectiveness and toxicity of ciprofloxacin vs an aminoglycoside, both in combination with a beta-lactam, for the treatment of febrile neutropenia in the inpatient setting. METHODS: For this meta-analysis of randomized controlled trials (RCTs) that compared the cipirofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination for the treatment of febrile neutropenia and reported data on effectiveness, mortality, and/or toxicity, we searched PubMed (1950-2004), Current Contents, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles, including review articles, as well as abstracts presented at international conferences. Data for 3 primary and 2 secondary outcome were extracted by 2 investigators. RESULTS: Eight RCTs were included in the analysis. Comparable or better outcomes were observed with the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination: clinical cure without modification of the initial regimen (odds ratio [OR], 1.32; 95% confidence interval [Cl], 1.00-1.74; P = .05), clinical cure in the subset of patients with documented infections (OR, 1.56; 95% Cl, 1.05-2.31; P = .03) all-cause mortality (OR, 0.85; 95% Cl, 0.54-1.35; P = .49), wlthdraw of the study drugs due to toxicity (OR, 0.87; 95% Cl, 0.57-1.12; P = .51), and nephrotoxicity (OR, 0.30; 95% Cl, 0.16-0.59; P < .01). The ciprofloxacin/beta-lactam combination was also associated with better clinical cure compared to the aminoglycoside/beta-lactam combination in the subset of RCTs with non-low-risk patients (C R, 1.38; 95% Cl, 1.01-1.88; P = .04), as well as in the subset of studies that included the same beta-lactam in both treatment arms (OR, 3.47; 95% Cl, 1.06-2.05; P = .02). CONCLUSION: The combination of ciprofloxacin with a beta-lactam antibiotic should be consider -d an important therapeutic option in hospitalized febrile neutropenic patients who have not received a quinolone for prevention of infections and in settings in which quinolone resistance is not common.