Background Although many global health programs focus on providing clinical care or medical education, improving clinical operations can have a significant effect on patient care delivery, especially in developing health systems without high-level operations management. Lean manufacturing techniques have been effective in decreasing emergency department (ED) length of stay, patient waiting times, numbers of patients leaving without being seen, and door-to-balloon times for ST-elevation myocardial infarction in developed health systems; but use of Lean in low to middle income countries with developing emergency medicine systems has not been well characterized. Objectives To describe the application of Lean manufacturing techniques to improve clinical operations at Komfo Anokye Teaching Hospital in Ghana and to identify key lessons learned to aid future global EM initiatives. Methods A three-week Lean improvement program focused on the hospital admissions process at Komfo Anokye Teaching Hospital was completed by a 14-person team in six stages: problem definition, scope of project planning, value stream mapping, root cause analysis, future state planning, and implementation planning. Results The authors identified eight lessons learned during our use of Lean to optimize the operations of an ED in a global health setting: 1) the Lean process aided in building a partnership with Ghanaian colleagues; 2) obtaining and maintaining senior institutional support is necessary and challenging; 3) addressing power differences among the team to obtain feedback from all team members is critical to successful Lean analysis; 4) choosing a manageable initial project is critical to influence long-term Lean use in a new environment; 5) data intensive Lean tools can be adapted and are effective in a less resourced health system; 6) several Lean tools focused on team problem solving techniques worked well in a low resource system without modification; 7) using Lean highlighted that important changes do not require an influx of resources; 8) despite different levels of resources, root causes of system inefficiencies are often similar across health care systems, but require unique solutions appropriate to the clinical setting. Conclusions Lean manufacturing techniques can be successfully adapted for use in developing health systems. Lessons learned from this Lean project will aid future introduction of advanced operations management techniques in low to middle income countries.