Human-centered design (HCD), an empathy-driven approach to innovation that focuses on user needs, offers promise for the rapid design of health care interventions that are acceptable to patients, clinicians, and other stakeholders. Reviews of HCD in healthcare, however, note a need for greater rigor, suggesting an opportunity for integration of elements from traditional research and HCD. A strategy that combines HCD principles with evidence-grounded health services research (HSR) methods has the potential to strengthen the innovation process and outcomes. In this paper, we review the strengths and limitations of HCD and HSR methods for intervention design, and propose a novel Approach to Human-centered, Evidence-driven Adaptive Design (AHEAD) framework. AHEAD offers a practical guide for the design of creative, evidence-based, pragmatic solutions to modern healthcare challenges.