Despite decades of research on the impact of interprofessional collaboration (IPC), we still lack definitive proof that team-based care can lead to a tangible effect on healthcare outcomes. Without return on investment (ROI) evidence, healthcare leaders cannot justifiably throw their weight behind IPC, and the institutional push for healthcare manpower reforms crucial for facilitating IPC will remain variable and fragmentary. The lack of proof for the ROI of IPC is likely due to a lack of a unifying conceptual framework and the over-reliance on the single-method study design. To address the gaps, this paper describes a protocol which uses as a framework the Quadruple Aim which examines the ROI of IPC using four dimensions: patient outcomes, patient experience, provider well-being, and cost of care. A multimethod approach is proposed whereby patient outcomes are measured using quantitative methods, and patient experience and provider well-being are assessed using qualitative methods. Healthcare costs will be calculated using the time-driven activity-based costing methodology. The study is set in a Singapore-based national and regional center that takes care of patients with neurological issues.