Background: In Ireland and across all continents, we are experiencing significant shifts in healthcare population profiles with longer life expectancies and people living with a myriad of chronic illnesses. Advanced nursing practice has been viewed as one ‘panacea’ for solutions to the healthcare crisis first established in Ireland in 2002. There is, however, a lack of understanding of advanced nurse practitioners (ANP) clinical autonomy. Aim: This study set out to explore the levels of clinical autonomy amongst ANPs in Ireland. Methods: A cross-sectional study design was used in a representative sample of ANPs in Ireland across the full range of healthcare settings. A bespoke quantitative survey instrument was developed and administered to the sample ANPs. This was informed by a literature review, an existing scale measuring ANP clinical autonomy and a new bespoke subscale developed for this study. As part of the survey, open comments about ANPs views of their clinical autonomy were captured and informed by thematic analysis. Results: One hundred and forty-eight ANPs completed the survey giving a response rate 33% of all ANPs Nationally. The findings illustrate high and extremely high levels of clinical autonomy impact in areas such as self-mastery, completing full episodes of care without a physician, discharging patients with or without a physician’s consultation and independently referring onwards to other specialists. ANPs clinical autonomy requires clear understanding and collaboration to reduce constraints to their role. Recommendation for Education: Educational strategies at the undergraduate and postgraduate levels should foster ANP self-determination and resilience approaches. Increasingly experienced ANPs with a hybrid ability between educational and ANP active clinical practice is essential to improve ANP clinical autonomy to its fullest capacity. Recommendation for Policy Makers: Encourage ANP structures with an ethos of embracing a generic advanced practice strategy rather than speciality or silo developments. Recommendation for Organisational Policy: All Irish Healthcare organisations and universities should encourage their full utilisation and realistically prepare future ANP clinical autonomy. Conclusion: This study underlines several fundamental motivators required to encourage, fully utilise and sustain clinical autonomy: competence, relatedness, and autonomy.