<p>Advances in educational research and technology provide educators and learning and development (L&amp;D) specialists with powerful tools to innovate health professions education (HPE) and address the relentless growth of content information. Yet, traditional practices often hinder the critical appraisal and application of evidence-based educational methods. While systematic models ground the instructional design of learning experiences in research and theory, they are frequently perceived as too rigid, time consuming, and resource intensive for widespread adoption in clinical education settings. This article introduces an agile, evidence-informed approach to instructional design tailored for HPE. The Agile eVidence-Informed Design (AVIDesign) model was developed to streamline the design and continuous improvement of educational interventions. AVIDesign aligns with evidence-based medicine by offering a systematic yet flexible process for designing instruction, incorporating design sprints, transdisciplinary collaboration, and contextually relevant appraisal of research evidence. We present the core principles and practices of AVIDesign, including strategies to right-size instructional design initiatives, formulate targeted LICO (Learner, Intervention, Context, Outcome) questions, appraise evidence using QSR (Quality, Strength, Relevance) criteria, and evaluate outcomes through formative and summative assessments. The application of AVIDesign is illustrated through three real-world design projects in HPE involving curriculum development, branching scenarios, and ePortfolio systems. Each case highlights how AVIDesign promotes compatibility, trialability, and reduced complexity to facilitate adoption. Key lessons learned from the projects are distilled to inform future applications of AVIDesign and guide continued research on agile, evidence-informed instructional design practices in health professions education. </p>