Background Decision-making on the reimbursement of cancer drugs by the Irish health service represents an area of high political and public health priority. This reflects the high cost and increasing volume of decision-making activities associated with new cancer drugs. The Irish National Cancer Strategy 2017-2026 calls for strengthening of the Irish decision-making process with respect to transparency and explicit procedures. This study analysed the current Irish process with respect to the characteristics ‘transparent’ and ‘systematic’ and aimed to identify potential opportunities for improvement. Within the spectrum of coverage decision-making, the focus was on committee-level reimbursement decision-making. Methods This mixed-methods study involved a comparative review of methods and process documents from within the Irish setting and under NICE, the England/Wales decision-making counterpart. Irish and international literature were also reviewed to identify relevant studies and expert opinion. Qualitative interviews were performed with stakeholders experienced in NICE decision-making processes. Results Processes of pharmacoeconomic evaluation were found to be guideline-driven and transparent in terms of communication of results. The point of committee-level decision-making, however, was found to lack transparency in both process (committee membership, conduct of meetings) and outcomes (publication of how individual decisions were made). Several opportunities exist to improve transparency, including release of relevant documentation to the public domain. Consistency could potentially be enhanced by the introduction of MCDA-like approaches or the introduction of other more explicit decision rules. However, such initiatives are limited by the resource-intensity of implementation and potential lack of acceptability to decision-makers. Recommendations Six key recommendations are presented. These largely consider the establishment of procedures and resources for the appropriate documentation and release of information to the public, and the leveraging of local expertise to focus on refinement of the drug reimbursement decision-making process, particularly regarding existing and potential decision rules.