Aim: To investigate the views of Nurse Practitioners (NPs) regarding the development of setting-specific opioid prescribing guidelines. Background: There has been a rise in opioid-related deaths and adverse events in Canada in recent years. Although NPs make up a significant opioid prescriber group, no Canadian setting-specific guidelines exist to help guide their opioid prescribing. Methods: Purposive sampling was used to select NPs practicing in inpatient settings. One-on-one semi-structured interviews were conducted virtually with 14 NPs (n=14) from Ontario. Directed qualitative content analysis was used to interpret interview data. Findings: The majority of NPs interviewed (n=13, 92.8%) believe that setting-specific opioid prescribing guidelines would benefit their practice. Interview responses illustrated that NPs face several challenges associated with inpatient opioid prescribing. To help mitigate these challenges, they often consult a pharmacist and reference prescribing resources such as Lexicomp and UpToDate. Additionally, several NPs in our study formulated their own setting-specific opioid prescribing resources to help guide their prescribing. Furthermore, NPs who had transitioned to acute care from a primary health care setting experienced a lack of confidence with opioid prescribing in a specialty setting. Conclusion: The development of setting-specific NP opioid prescribing guidelines in Canada can improve the prescribing process for NPs by providing them with clear, evidence-based recommendations, thus reducing ambiguity and promoting positive patient outcomes. Future research should explore the possibility of adapting internationally published setting-specific opioid prescribing guidelines for Canadian practice and the unique opioid prescribing challenges NPs experience when transitioning from primary care to acute care settings.