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Introduction The WHO neglected tropical disease (NTD) roadmap stresses the importance of integrating NTDs requiring case management (CM) within the health system. The NTDs programme of Liberia is among the first to implement an integrated approach and evaluate its impact.Methods A retrospective study of three of five CM-NTD-endemic counties that implemented the integrated approach was compared with cluster-matched counties with non-integrated CM-NTD. We compared trends in CM-NTD integrated versus non-integrated county clusters. We conducted a pre-post comparison of WHO high-level outcomes using data collected during intervention years compared with baseline in control counties. Changes in health outcomes, effect sizes for different diseases and rate ratios with statistically significant differences were determined. Complementary qualitative research explored CM-NTD stakeholders’ perceptions, analysed through the framework approach, which is a transparent, multistage approach for qualitative thematic interdisciplinary data analysis.Results The detection rates for all diseases combined improved significantly in the intervention compared with the control clusters. Besides leprosy, detection rates improved with large effects, over fourfold increase with statistically significant effects for individual diseases (p