INTRODUCTION: Very few pragmatic and community-level effectiveness trials integrate the use of qualitative research over all stages of the trial, to inform trial design, implementation optimization, results interpretation and post-trial policy recommendations. This is despite the growing demand for mixed methods research from funding agencies and awareness of the vital importance of qualitative and mixed methods research for understanding trial successes and challenges. DISCUSSION: We offer examples from work we have been involved in to illustrate how qualitative research conducted within trials can reveal vital contextual factors that influence implementation and outcomes, can enable an informed adaptation of trials as they are being conducted and can lead to the formulation of theory regarding the social and behavioural pathways of intervention, while also enabling community engagement in trial design and implementation. These examples are based on published findings from qualitative studies embedded within two ongoing large-scale studies demonstrating the population-level impacts of universal HIV testing and treatment strategies in southern and eastern Africa, and a qualitative study conducted alongside a clinical trial testing the adaptation, acceptability and experience of short-cycle therapy in children and adolescents living with HIV. CONCLUSIONS: We advocate for the integration of qualitative with clinical and survey research methods in pragmatic clinical and community-level trials and implementation studies, and for increasing visibility of qualitative and mixed methods research in medical journals. Qualitative research from trials ideally should be published along with clinical outcome data, either integrated into the "main" trial papers or published concurrently in the same journal issue. Integration of qualitative research within trials can help not only to understand the why behind success or failure of interventions in different contexts, but also inform the adaptation of interventions that can facilitate their success, and lead to new alternative strategies and to policy changes that may be vital for achieving public health goals, including the end of AIDS.