A new process called Lean Healthcare Systems Engineering (LHSE) recently invented for improving healthcare workflows and designing new care is reviewed and compared to previous quality initiatives: PDSA, TQM, Six Sigma, Lean, Theory of Constraints, and several others. LHSE is applicable to workflow improvement or new care design projects in clinical environments, including hospitals, operating suites, emergency departments, clinics, imaging and clinical laboratories, pharmacies, population health, and telemedicine. LHSE integrates the strengths of Lean Six Sigma and Systems Engineering (SE). Lean’s overarching philosophy of “do what is necessary to deliver the value and reject everything else as waste” governed the tailoring of the classical SE process to healthcare, eliminating the many bureaucratic and wasteful activities, and leaving only the steps that truly are needed in healthcare improvement projects. Utilizing tools from SE, LHSE presents several powerful improvements over previous approaches, in particular system optimization reducing the trial-and-error effort and cost; and increasing the predictability of outcomes. LHSE provides consistent logical rigor to projects, reducing iterations and failure, and is particularly effective in elimination the notorious fragmentation in healthcare systems.