OBJECTIVES: To investigate the extent to which the convenience offered by fixed-dose combination preparations is valued by payers when performing Health Technology Assessments (HTA). METHODS: Publication lists of major European HTA agencies (SMC, HAS, IQWiG, NICE, UVEF, AHTAPoL, TLV, CVZ) were searched manually for appraisals on fixed-dose combination drugs from 2010 onwards. Of the agencies that published assessments, the payers’ perception of fixed-dose combination regarding their potential of improving adherence was evaluated. The investigation focused on three large therapeutic areas: diabetes, hypertension, rheumatoid arthritis. RESULTS: We identified 135 assessments of diabetes (61), hypertension (36), and rheumatoid arthritis (38) medications. 11 HTAs assessed fixed-dose combination preparations. Of these, 9 HTAs, conducted by two agencies (SMC and HAS), provided insights on adherence and ease of use. While SMC in general recognizes the potential advantage of fixed-dose combination to reduce a patient’s pill burden at no additional or moderately higher costs, clinical trials did not provide any proof. Issues seen were differences in recommended dosing levels between the normal formulations and the fixed-dose preparations, exhibiting potential safety risks to be weighed against potential benefits. Likewise, HAS could not find a benefit of fixed-dose over free dose combinations in terms of efficacy and quality of life. In addition, HAS holds the opinion that dose combinations of more than two drugs strongly limit individual up-titration, and may lead to over-prescribing and misuse, thereby making the medical benefit insufficient for reimbursement. CONCLUSIONS: Adherence is inversely related to the number of doses per day, and poor adherence is the primary reason for sub-optimal clinical benefit, reduces patient’s quality of life and wastes health-resources. Although fixed-dose combination preparations can significantly increase patient adherence, our analysis showed that HTA agencies would only recognize the value of fixed-dose combinations for reimbursement decisions if clinical proof of superior adherence was available.