Background The national clinical programmes (NCPs) were established in 2010 to achieve three objectives, namely: improve quality, access and cost effectiveness. Limited research exists on their implementation in the Republic of Ireland (ROI). This qualitative study identified key stakeholders’ perceptions on (a) implementation thus far, and (b) conditions perceived necessary for implementation in acute hospitals. Aims The overall aim of this research was to undertake an in-depth study to explore from the perspectives of key stakeholders, their perceptions on implementation of the national clinical programmes, thus far, in relation to three overarching objectives (to improve quality, access, cost effectiveness) and what are the conditions necessary for their implementation in the Republic of Ireland's acute hospitals. Methods Twenty participants were interviewed using face-to-face audio-recorded semi-structured interviews. Transcribed data were coded and analysed, and a number of themes emerged from the dataset relating to the study aims. Results Implementation was perceived as being inconsistent. Outcomes were identified as: best practice guidelines, models of care, protocols, pathways; education & training; new services; improved discharges; improved patient outcomes; reduced length of stay; timely access; reduced waiting lists; cost effectiveness and other intangible outcomes. Sixteen conditions, under four themes, were perceived necessary for implementation, namely: Governance – structure, audit & monitoring, senior management support, accountability, and clear objectives and expectations; Communication – visible face-to-face engagement, internal awareness, and external awareness; Leadership – programme level, national level, hospital level, and professional level; Resources – budget, staff, information technology, training, skills, and competency. Conclusions This study adds to the existing limited body of knowledge on implementation of the NCPs in the acute hospitals in the ROI while contributing to the wider international literature in this area. The study provides hitherto unreported knowledge on the conditions that are perceived necessary for implementation. Novel in the ROI context is the perceived necessity to condense the number of NCPs, placing greater emphasis on (a) the need to structurally integrate the NCPs across the continuum of care, and (b) the importance of communication through visible face-to-face engagement. This study concludes that significant progress has been made by the NCPs towards meeting the objectives, albeit to varying degrees. There is a strong perception that the NCPs should remain, and that addressing the conditions perceived necessary for implementation in the areas of governance, communications, leadership and resources by both top-down senior health officials and bottom-up front-line hospital staff would significantly enhance the ability of the NCPs to meet objectives and implementation. It provides the ROI health services with valuable information to inform future reform, strategic planning and NCP implementation.