In several ways, randomized controlled trials represent a high standard of rigor in clinical biomedical research. Randomized controlled trials fail, however, to yield knowledge applicable to specific individuals. This article presents a methodological rationale for a mixed methods approach to n-of-1 clinical studies that attends to the preferences and concerns of individuals while attaining high standards of qualitative and quantitative rigor. An illustrative research design involving a hypothetical music therapy intervention for a quality of life outcome is examined in some detail and a concluding argument is made that the proposed mixed methods approach is especially appropriate for early-stage research interventions intended to generate explanatory hypotheses.