Background: Infection in cancer children is a great problem as the child who does not die from the cancer may die from infection. So infection in neutropenic patient should be treated seriously usually by third generation cephalosporin combined with aminoglycosides as a first line of antibiotic. The cephalosporins are progressively losing their reliability because of Enterobacter and cetrobacter species, which over express type 1 B-lactamase that confer resistance. So when the first line of antibiotic fails to control the fever, carbapenem group of antibiotics are used as a second line of antibiotic in combination with aminoglycosides. Carbapenem group covers certain pathogens, which are not covered by third generation cephalosporins. It is also more stable to B-lactamase in relation to currently available B-lactam antibiotics. And in addition to other activity against gram-negative aerobes, it acts against many gram-positive aerobes and most anaerobic organisms especially clindamycin resistant species.Methods: febrile granulocytopenic children with leukemia, lymphoma or solid tumors after chemotherapy were included in an open, prospective, randomized, single-center study comparing imipenem/cilastatin versus meropenem as a second line of antibiotics. The response rates are assessed clinically and microbiologically. Assessment of side effects was supplemented by specific definitions. Results: 104 febrile neutropenic episodes were enrolled in this study. 61 patients with 66 (63.4%) high-risk febrile granulocytopenia episodes were considered eligible. 38 episodes were excluded from the study. The duration of using imipenem/cilastatin and meropenem as second line of antibiotic was nearly equal, 6.82 days, 7.48 days in arm A and B respectively. Time to control fever in both groups was 1.15 days, 1.12 days in arm A and B respectively. Gram-negative organisms are slightly predominant where they represent 9 organisms from total isolates in group A (56.25% of isolates), and 5 organisms from total isolates in group B (50% of isolates).Conclusion: Imipenem/Cilastatin and Meropenem are highly effective in the treatment of fever in neutropenic patients as a second line after failure of first line of antibiotics, producing a high rate of clinical and bacteriological response. Although meroprnem show some resistance against certain bacteria as Enterobacter cloacae, and although imipenem/cilastatin can not be used in patients with CNS abnormalities, both of them showed equivalent efficacy and tolerability without significant difference.