The value of qualitative evidence synthesis for informing healthcare policy and practice within evidence-based medicine is increasingly recognised. However, there is a lack of consensus regarding how to judge the methodological quality of qualitative studies being synthesised and debates around the extent to which such assessment is possible and appropriate. The Critical Appraisal Skills Programme (CASP) tool is the most commonly used tool for quality appraisal in health-related qualitative evidence syntheses, with endorsement from the Cochrane Qualitative and Implementation Methods Group. The tool is recommended for novice qualitative researchers, but there is little existing guidance on its application. This article considers issues related to the suitability and usability of the CASP tool for quality appraisal in qualitative evidence synthesis in order to support and improve future appraisal exercises framed by the tool. We reflect on our practical experience of using the tool in a systematic review and qualitative evidence synthesis. We discuss why it is worth considering a study’s underlying theoretical, ontological and epistemological framework and how this could be incorporated into the tool by way of a novel question. We consider how particular features of the tool may impact its interpretation, the appraisal results and the subsequent synthesis. We discuss how to use quality appraisal results to inform the next stages of evidence synthesis and present a novel approach to organise the synthesis, whereby studies deemed to be of higher quality contribute relatively more to the synthesis. We propose tool modifications, user guidance, and areas for future methodological research.