Introduction: Intravenous therapy and medicines (IVTM) are the most common invasive interventions in use in healthcare. Prescribed IVTM play an essential role in the treatment of illness, management of chronic conditions and in maintaining health and wellbeing. The intravenous (IV) route is the administration of concentrated medications (diluted or undiluted) directly into peripherally or centrally inserted vascular access devices. Medication safety is a key priority and best practice standards are required to guide the safe preparation and administration of IVTM. Methods: We will conduct a systematic review of the literature pertaining to the preparation and administration of intravenous therapy and medicines. Our search will include studies concerned with the preparation and/or administration of IVTM via peripheral or central vascular access devices. We will be guided by the preferred reporting items for systematic review and meta-analysis (PRISMA) in this review. Literature will include all trial designs, national/international guidelines, and expert consensus opinion made available in English from 2009 to present day. Conclusions: We will synthesise the evidence concerning safe and effective preparation and administration of intravenous therapy and medicines to inform the development of a national guideline for healthcare professionals in Ireland. The availability of up-to-date, contemporaneous evidence-based practice standards will ensure quality and safety for service-users. Registration:  This study has been submitted to PROSPERO and we are awaiting confirmation of registration.