Evaluating interventions in palliative care using randomized controlled trials (RCTs) has helped advance the specialty and create an evidence base for the delivery of care. RCTs, however, are notoriously difficult to conduct in palliative care, raising a variety of practical, ethical and moral dilemmas. Mixed-methods research, which combines qualitative research and RCTs, offers a potential solution to these problems. This paper begins by examining the theoretical basis for combining the two approaches, before reviewing the specific role qualitative research could play in planning, conducting and implementing trials. The paper then goes on to explore how palliative care research currently uses the mixed-methods approach, by searching the trials included in six Cochrane Systematic Reviews (n = 146) on the incorporation of qualitative research. Only one trial undertook qualitative research. These findings reflect some of the challenges facing mixed-methods research, which include lack of experience in a research team, the problems of obtaining funding and difficulties in publishing. The paper concludes that while combining qualitative and quantitative research is not a panacea for methodological problems in palliative care research, with careful planning and integration, the approach may enhance the clinical and ethical utility of trial findings, which in turn will improve patient care.