Abstract Background While the world has made much global progress toward the reduction of new HIV infections, HIV continues to be an important public health problem. In the face of constantly constrained resources, donors and grantees alike must seek to optimize resources and deliver HIV services as efficiently as possible. While there is evidence that management practices can affect efficiency, this has yet to be rigorously tested in the context of HIV service delivery. Methods The present protocol describes the design of a cluster-randomized control trial to estimate the effect of management practices on efficiency. Specifically, we will evaluate the impact of an intervention focused on improving management practices among community-based organizations (CBOs), on the costs of HIV prevention services for female sex workers (FSW) in Nigeria. To design the intervention, we used a qualitative, design thinking-informed methodology that allowed us to understand management in its organizational context better and to develop a user-centered solution. After designing the suite of management tools, we randomly assigned 16 CBOs to the intervention group, and 15 CBOs to the control group. The intervention consisted of a comprehensive management training and a management “toolkit” to support better planning and organization of their work and better communication between CBOs and community volunteers. Both treatment and control groups received training to record data on efficiency—inputs used, and outputs produced. Both groups will be prospectively followed through to the end of the study, at which point we will compare the average unit cost per FSW served between the two groups using a quasi-experimental “difference-in-differences” (DiD) strategy. This approach identifies the effect of the intervention by examining differences between treatment and control groups, before and after the intervention thus accounting for time-constant differences between groups. Despite the rigorous randomization procedure, the small sample size and diversity in the country may still cause unobservable characteristics linked to efficiency to unbalanced between treatment and control groups at baseline. In anticipation of this possibility, using the quasi-experimental DiD approach allows any baseline differences to be “differenced out” when measuring the effect. Discussion This study design will uniquely add to the literature around management practices by building rigorous evidence on the relationship between management skills and practices and service delivery efficiency. We expect that management will positively affect efficiency. This study will produce valuable evidence that we will disseminate to key stakeholders, including those integral to the Nigerian HIV response. Trial registration This trial has been registered in Clinical Trials (NCT03371914). Registered 13 December 2018