BACKGROUND: Mobile health (mHealth) has the potential to improve access to healthcare, especially in developing countries. The proliferation of mHealth has not been accompanied by a corresponding growth in design guidelines for mHealth applications. This paper proposes a framework for mHealth application design that combines the Information Systems Research (ISR) framework and design thinking. We demonstrate a use case for the proposed framework in the form of an app to read the result of the tuberculin skin test (TST), which is used to screen for latent tuberculosis infection. The framework was used in the re-design of the TST reading app but could also be used in earlier stages of mHealth app design. METHODS: The ISR framework and design thinking were merged based on how the modes of design thinking integrate with the cycles of the ISR framework. Using the combined framework, we re-designed an mHealth app for TST reading, intended to be used primarily in a developing context by healthcare workers. Using the proposed framework, the app was iterated upon and developed with the aid of personas, observations, prototyping and questionnaires. RESULT: The combined framework was applied through engagement with end-users, namely ten healthcare workers and ten graduate students. Through review of the literature and iterations of the app prototype, we identified various usability requirements and limitations. These included challenges related to image capture and a misunderstanding of instructions. These insights influenced the development and improvement of the app. CONCLUSION: The combined framework allowed for engagement with end-users and for low-cost, rapid development of the app while addressing contextual challenges and needs. The integration of design thinking modes with the ISR cycles was effective in achieving the objectives of each approach. The combined framework acknowledges the importance of engaging users when implementing mHealth technologies, especially in developing and under-resourced contexts. Findings from this study support the use of this framework as a guide in the design of user-centred mHealth interventions.