OBJECTIVES: To highlight the impact of tolerability profiles on Health Technology Assessment (HTA) decision making in non-small cell lung cancer (NSCLC), ovarian cancer and prostate cancer from three European HTA agencies. METHODS: HTA assessments on NSCLC, ovarian cancer and prostate cancer products marketed since 2011 were selected from HAS (France), G-BA (Germany) and NICE (UK). 14 reports on NSCLC, 5 on ovarian cancer and 14 on prostate cancer were selected for in-depth analysis. RESULTS: In the UK, safety profiles of the investigated drugs did not seem to have major impact on the recommendation. It was however seen that drugs with a good safety profile were more often recommended. Low impact of safety outcomes on the final decision from NICE was, for example, seen in the assessment of afatinib, where a significant increase in serious adverse events did not negatively impact the recommendation because clinical benefits outweighed safety concerns. Safety data and patient-relevance of endpoints is of high importance in Germany. A beneficial safety profile resulted in a higher benefit rating, whereas a negative safety profile lowered the G-BA rating. Case examples are evaluations of afatinib and crizotinib, where a negative safety profile lowered the benefit rating. Efficacy outcomes were weighted against safety outcomes in all assessments in France. An unfavourable safety profile appeared to have a negative impact on the ASMR rating from HAS, while a favorable profile did not have a positive impact. An example is the assessment of cabazitaxel, where the safety data presented at the initial submission was unfavorable, resulting in a lower ASMR rating (IV), however a resubmission with additional safety data resulted in a higher rating (III). CONCLUSIONS: Different EU payers seem to have a different view on safety profiles, with the highest impact seen in Germany and the lowest impact seen in the UK.