Abstract Background Psoriatic arthritis (PsA) presents a unique clinical challenge. Affecting joints, skin, nails, and other organs, it is associated with various comorbidities and has a significant impact on quality of life, social participation and working life. While biologic and other targeted synthetic disease modifying anti-rheumatic drugs (bDMARDs and tsDMARDs) have revolutionised therapy, questions remain about the long-term safety of these agents, and their effectiveness and cost-effectiveness in the real-world clinical setting. Methods/design The British Society for Rheumatology Psoriatic Arthritis Register (BSR-PsA) is a prospective registry of patients with PsA, recruited from across Great Britain, who are (a) commencing a bDMARD/tsDMARD; or (b) naïve to all bDMARDs/tsDMARDs. Ethical approval was given by the NHS West of Scotland Research Ethics Committee 3 (reference: 18/WS/0126). Clinical data are extracted from participants’ medical records, including symptom onset and diagnosis, joint, skin and nail symptoms, dactylitis and enthesitis. Physical measurements (height, weight and 66/68 joint counts) and a detailed drug history are taken. Participants are also asked to complete questionnaires comprising instruments relating to general health and quality of life, axial disease, sleep and fatigue, impact of disease, functional status, mental health, other symptoms, and occupational status. The study duration is 5 years in the first instance, and all participants are followed up annually until the end of the study. Participants commencing a bDMARD/tsDMARD are also followed up three and six months after the start of therapy. Disease activity, including C-reactive protein, is assessed at each visit; and participants from some centres are invited to donate blood and urine samples for the creation of a biobank. Discussion Complementing data from randomised trials, results from this study will contribute to the evidence base underpinning the clinical management of psoriatic arthritis. Various analyses will determine the effectiveness and safety of bDMARDs/tsDMARDs in the real-world, will examine the clinical and biological predictors of treatment response, and will provide real-world data on the cost-effectiveness of these therapies, as well as providing informative data important to patients such as quality of life and occupational outcomes. Trial registration The full study protocol is registered on the Open Science Framework (https://osf.io/jzs8n).