BACKGROUND: Timely and appropriate management of febrile illness among children under five years of age will contribute to achieving Millennium Development Goal-4. The revised World Health Organization-Global Malaria Programme's policy on test-based management of malaria must integrate effectively into the Integrated Management of Childhood Illness (IMCI). This study reports on perceptions of health workers on the health system factors influencing effective delivery of test-based diagnosis of malaria with IMCI. METHODS: A qualitative study was conducted among a range of health workers at different levels of the health system in the Brong Ahafo Region of Ghana. Interview transcripts were transferred into Nvivo 8 software for data management and analysis. A frame-work approach at two levels was used in the analysis, which included the processes required for implementation of test-based management of malaria and the health systems context. RESULTS: Forty-nine in-depth interviews were conducted. The National Health Insurance Scheme (NHIS) was perceived to have led to an increase in health facility attendance, thereby increasing the workload of health workers. Workload was reported as the main reason that health workers were not able to complete all of the examinations included in the IMCI algorithm. The NHIS financing guidelines were seen to be determining diagnosis and treatment practices by health-care givers. Concern was expressed about the erratic supply of malaria rapid diagnostic test kits (RDTs), the quality of RDTs related to potential false negative results when clinical symptoms were consistent with malaria. IMCI was seen as important but practically impossible to fully implement due to workload. CONCLUSIONS: Implementation of the WHO-revised IMCI guideline is confronted with a myriad of health systems challenges. The perceptions of front-line health workers on the accuracy and need for RDTs together with the capacity of health systems to support implementation plays a crucial role. The NHIS financing guidelines of diagnostics and treatments are influencing clinical decision-making in this setting. Further study is needed to understand the impact of the NHIS on the feasibility of integrating test-based management for malaria into the IMCI guidelines.