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Abstract Background A guideline contains processes and procedures intended to guide health service delivery. However, the presence of guidelines may not guarantee their implementation, which may be a result of weaknesses in the development process. This study was undertaken to describe the processes of developing health planning, services management, and clinical guidelines within the health sector in Uganda, with the goal of understanding how these processes facilitate or abate the utility of guidelines. Methods Qualitative and quantitative research methods were used to collect and analyze data. Data collection was undertaken at the levels of the central Ministry of Health, the district, and service delivery. Qualitative methods included review of documents, observations, and key informant interviews, as well as quantitative aspects included counting guidelines. Quantitative data were analyzed with Microsoft Excel, and qualitative data were analyzed using deductive content thematic analysis. Results There were 137 guidelines in the health sector, with programs related to Millennium Development Goals having the highest number (n = 83). The impetus for guideline development was stated in 78% of cases. Several guidelines duplicated content, and some conflicted with each other. The level of consultation varied, and some guidelines did not consider government-wide policies and circumstances at the service delivery level. Booklets were the main format of presentation, which was not tailored to the service delivery level. There was no framework for systematic dissemination, and target users were defined broadly in most cases. Over 60% of guidelines available at the central level were not available at the service delivery level, but there were good examples in isolated cases. There was no framework for systematic monitoring of use, evaluation, and review of guidelines. Suboptimal performance of the supervision framework that would encourage the use of guidelines, assess their utilization, and provide feedback was noted. Conclusions Guideline effectiveness is compromised by the development process. To ensure the production of high-quality guidelines, efforts must be employed at the country and regional levels. The regional level can facilitate pooling resources and expertise in knowledge generation, methodology development, guideline repositories, and capacity building. Countries should establish and enforce systems and guidance on guideline development.