OBJECTIVES: The clinical endpoints selected for oncology trials have to meet the needs of diverse stakeholders: patients, clinicians, regulators, and HTA agencies, each with a different perspective. PFS is becoming a more widely accepted measure of treatment efficacy, but there is tension between regulators and payors regarding its acceptability.  This study investigated PFS as a valid and credible endpoint from the perspectives of relevant decision-makers. METHODS: Published and gray literature (2005–2015) were searched for regulatory and HTA guidance on PFS as an endpoint. We  identified examples of decisions by regulators and HTA agencies in which PFS was the primary endpoint, and compared the assessments.  RESULTS: Guidance from regulatory and HTA agencies indicates  the suitability of PFS as an endpoint depends on the cancer type and stage, seen in  assessments of afatinib and erlotinib in non-small cell lung cancer  and bevacizumab in ovarian cancer: FDA and EMA approvals were based on PFS data. However, the TC in France awarded ASMR IV for erlotinib and bevacizumab and ASMR V for afatinib. NICE in the UK approved afatinib and erlotinib based on additional interim OS data and a patient access scheme; bevacizumab was not approved because of  uncertainty in translating PFS gain to OS. CONCLUSIONS: PFS is a valid and credible endpoint in many oncology trials. However, differences in stakeholder perspectives and evidentiary requirements may mean that products approved on the basis of PFS data face delays in HTA or protracted pricing negotiations, or are rejected for reimbursement. PFS as an endpoint allows shorter trials , efficiency is improved, and fewer patients are exposed to an investigational drug. The limitations associated with PFS as an endpoint are largely manageable. Thus, the value and relevance of PFS needs to be recognized consistently across HTA agencies, and approaches harmonized between HTA agencies and regulators.