Background: We examined the similarities and differences between studies using two common metrics used in cost-effectiveness analyses (CEAs): cost per quality-adjusted life years (QALYs) gained and cost per disability-adjusted life year (DALY) averted. Methods: We used the Tufts Medical Center CEA Registry, which contains English-language cost-per-QALY gained studies, and Global Cost-Effectiveness Analysis (GHCEA) Registry, which contains cost-per-DALY averted studies. We examined study characteristics including intervention type, sponsor, country, and primary disease, and also analysed the number of CEAs versus disease burden estimates for major diseases and conditions across three geographic regions. Results: We identified 6,438 cost-per-QALY and 543 cost-per-DALY studies published through 2016 and observed rapid growth in publication rates for both literatures. Cost-per-QALY studies were most likely to examine pharmaceuticals and interventions in high-income countries. Cost-per-DALY studies predominantly focused on infectious disease interventions and interventions in low and lower-middle income countries. We found discrepancies in the number of published CEAs for certain diseases and conditions in certain regions, suggesting “under-studied” areas (e.g., cardiovascular disease in Southeast Asia, East Asia, and Oceania and “overstudied” areas (e.g., HIV in Sub Saharan Africa) relative to disease burden in those regions. Conclusions: The number of cost-per QALY and cost-per-DALY analyses has grown rapidly with applications to diverse interventions and diseases. Discrepancies between the number of published studies and disease burden suggest funding opportunities for future cost-effectiveness research.