Background <p>Some people experience side-effects from medicines which can lead to negative patient outcomes and increased NHS costs. Pharmacogenetic-guided prescribing supports the safety and effectiveness of medicines. The Pharmacogenetics Roll Out – Gauging Response to Service (PROGRESS) study is assessing the viability and utility of pharmacogenetic-guided prescribing in general practice. We conducted a parallel process evaluation to explore the barriers and enablers to implementing pharmacogenetic-guided prescribing in general practice, from a clinician perspective.</p> Methods <p>Twenty-nine online semi-structured interviews were conducted with 30 general practice staff across 20 sites in England implementing the PROGRESS study. We used a modified framework approach to analyse the data, informed by the Consolidated Framework for Implementation Research and Normalisation Process Theory.</p> Findings <p>Clinicians saw value in offering pharmacogenetic-guided prescribing in general practice, but limited testing to where they perceived it provided greatest benefit. There was limited evidence of practices planning for implementation beyond setting up the PROGRESS study. Sites tailored delivery of pharmacogenetics to their local practice context, which acted as an enabler to implementation. Delivering pharmacogenetic-guided prescribing within the confines of a research study and clinicians’ workload acted as barriers to implementation.</p> Conclusion <p>General practice staff understood the value and purpose of pharmacogenetic-guided prescribing, but there was little evidence of wider practice involvement beyond raising awareness among staff. PROGRESS involvement was viewed as more as proof of concept for research purposes, rather than normalising pharmacogenetics into routine practice.</p>