BACKGROUND: Up to one-third of people living with psoriasis develop psoriatic arthritis (PsA), and the majority have active psoriasis prior to the development of arthritis. Clinical risk factors, such as nail involvement, in conjunction with novel blood biomarkers, could improve PsA risk monitoring and early diagnosis. OBJECTIVES: The aim of the HIPPOCRATES Prospective Observational Study (HPOS-www.hpos.study) is to follow a cohort living with psoriasis and identify risk factors for the development of PsA. DESIGN: HPOS is a patient-driven online prospective European observational cohort. METHODS: Adult participants with psoriasis but with no prior diagnosis of PsA are eligible. Participants are invited to provide consent and join the study online. They complete a semi-structured questionnaire to collect data on demographics, psoriasis, comorbidities, risk factors for PsA, and the Psoriasis Epidemiology Screening Tool screening questionnaire. Follow-up is conducted through a questionnaire every 6 months. The primary outcome is the new onset of PsA confirmed by a diagnosis from their doctor. The study will also collect peripheral blood samples from a subset of participants for biomarker identification. ETHICS: This study follows the principles of the Declaration of Helsinki. To date, ethical approval has been granted by independent ethical committees in 10 countries. DISCUSSION: Studying a cohort of individuals with psoriasis will allow us to identify risk factors for arthritis development and to develop a risk calculator. This can support focused efforts on screening, patient education, and even studies looking to delay or prevent the onset of arthritis. This study, run via remote online data collection, provides an efficient way to recruit a large cohort (25,000) across multiple countries. However, challenges have had to be addressed with some key changes in study design, ethical review, and recruitment strategies required for each individual country. TRIAL REGISTRATION: HPOS, Clinicaltrials.gov ID: NCT05858528, IRAS number 325080; https://clinicaltrials.gov/study/NCT05858528?locStr=United%20Kingdom&country=United%20Kingdom&cond=Psoriasis&term=HPOS&aggFilters=status%3Anot%20rec&rank=1.