OBJECTIVES: Scientific research suggests that randomized controlled trials terminated early for benefit considerations systematically overestimate treatment effects of the primary outcome. This study assessed whether Health Technology Assessment (HTA) agencies accept the increased uncertainty around overall survival (OS) estimates in oncology trials arising from early termination. METHODS: Public scientific databases were searched to identify scientific articles and pivotal trials involving early trial termination. A selection of related HTA appraisals, published between January 2011 and February 2014, were analysed. Current scientific evidence on the impact of early stopping on outcome estimates was compared to the conclusions made by 11 HTA agencies. RESULTS: Twelve scientific articles, 12 pivotal trials, and 31 related HTA appraisals were selected for in-depth analysis. The scientific literature suggests that more stringent significance levels in the repeated interim analyses reduce the probability of finding significant results due to chance while large numbers of outcome events reduce the overestimation of treatment effects. Our analysis finds that a statistically significant gain in OS is an important decision driver for even the most critical HTA agencies, although the treatment effect may still be questioned when the trial is unblinded early. HTA agencies appreciate to receive the latest available information (UK, Australia and Germany) and may reject the use of oncology drugs when there is too much uncertainty around OS estimates to justify the proposed price.  It is generally useful to continue data collection and follow-up patients should HTA agencies still request more reliable OS estimates for modeling purposes (UK and Australia) or long-term risk-benefit evaluation (France). CONCLUSIONS: Payers are aware of the overestimation of effect size due to early trial termination and may reject drugs for high uncertainty around OS estimates. For adequate responses to requests for more reliable data, it is advised to continue data collection and follow-up patients.