ObjectivesBuilding an efficient health technology assessment (HTA) system requires significant effort and political commitment, in addition to human and financial resources. Expectations of what HTA can offer to middle-income countries (MICs) are continuously rising, which drives health policymakers to raise the question of whether HTA could help secure the financial sustainability needed to implement universal health coverage. In this study, we explored the impact HTA adoption may have on the countries and its impact on health system objectives, as well as transferability of benefits and drawbacks observed in higher-income to middle-income countries. MethodsWe utilized secondary data from a systematic literature review and primary data by disseminating a survey among local stakeholders in three MICs across three continents to capture their perspective on the impact of HTA implementation from a local context. ResultsIt was evident from the results of both the literature review and survey that the positive impacts of HTA implementation outweigh the negative impacts. Most of the reviewed literature discussed the impact of HTA on the intermediate objectives of the health finance policy in relation to the broad health system goals. According to the survey respondents, the most evident benefit of HTA implementation is improving the transparency and accountability of healthcare decisions. ConclusionsOverall, HTA implementation can introduce a myriad of benefits to healthcare systems in MICs as well. Our findings show that while HTA implementation may have the potential to generate cost savings in specific areas, there is no guarantee that HTA can generate savings at the macro level. Public Interest SummaryHealth technologies (medicines, devices, and interventions) are rapidly increasing in complexity and cost. Health Technology Assessment (HTA) guides healthcare decision-makers in choosing the most suitable, effective, affordable, and acceptable health technology to invest limited healthcare resources. However, healthcare decision-makers in middle-income countries (MICS) are still uncertain about whether adopting HTA would help them achieve the financial sustainability needed to achieve universal health coverage. Thereforewe sought to gather evidence on how HTA has affected the health systems of countries that have already adopted it by reviewing published research reports. In addition, healthcare decision-makers from three MICs were questioned about their perception of how HTA implementation will affect their country's health system. Wefound that the positive effects of HTA implementation outweigh the negative ones; specifically, the transparency and accountability of decisions are improved. However, although HTA implementation may generate cost savings in specific areas, it may not significantly contribute to overall financial sustainability.