Caring for patients with low-acuity conditions in Emergency Departments (ED) is often thought to cost more than treating those patients in other ambulatory settings. Understanding the relative cost of care between settings has critical implications for healthcare policy and system design. We conducted a systematic review of papers comparing the cost of care for low-acuity and ambulatory care sensitive conditions in ED and other outpatient settings. We searched PubMed, EMBASE, CINAHL, and Web of Science for peer reviewed papers, plus Google for grey literature. We conducted duplicate screening and data extraction, and quality assessment of included studies using an adapted SIGN checklist for economic studies. We calculated an unweighted mean charge ratio across studies and summarized our findings in narrative and tabular format. We identified one study comparing costs. 18 studies assessed physician or facility charges, conducted in the United States, United Kingdom, and Canada, including cohort analyses (5), charge analyses (5), survey (1), and database searches (5) assessing populations ranging from 370 participants to 60 million. Charge ratios ranged from 0.60 to 13.45 with an unweighted mean of 4.20. Most (12) studies were of acceptable quality. No studies since 2001 assess the comparative costs of ED versus non-ED care for low-acuity ambulatory conditions. Physician and facility charges for ED care are higher than in other ambulatory settings for low-acuity conditions. Empirical evidence is lacking to support that ED care is more costly than similar care in other ambulatory settings.