IntroductionMusculoskeletal (MSK) conditions constitute the highest burden of disease globally, with healthcare services often utilised inappropriately and overburdened. The aim of this trial is to evaluate the effectiveness of a novel clinical PAthway of CarE programme (PACE programme), where care is provided based on people’s risk of poor outcome.Methods and analysisMulticentre randomised controlled trial. 716 people with MSK conditions (low back pain, neck pain or knee osteoarthritis) will be recruited in primary care. They will be stratified for risk of a poor outcome (low risk/high risk) using the Short Form Örebro Musculoskeletal Pain Screening Questionnaire (SF-ÖMSPQ) then randomised to usual care (n=358) or the PACE programme (n=358). Participants at low risk in the PACE programme will receive up to 3 sessions of guideline based care from their primary healthcare professional (HCP) supported by a custom designed website (mypainhub.com). Those at high risk will be referred to an allied health MSK specialist who will conduct a comprehensive patient-centred assessment then liaise with the primary HCP to determine further care. Primary outcome (SF 12-item PCS) and secondary outcomes (eg, pain self-efficacy, psychological health) will be collected at baseline, 3, 6 and 12 months. Cost-effectiveness will be measured as cost per quality-adjusted life-year gained. Health economic analysis will include direct and indirect costs. Analyses will be conducted on an intention-to-treat basis. Primary and secondary outcomes will be analysed independently, using generalised linear models. Qualitative and mixed-methods studies embedded within the trial will evaluate patient experience, health professional practice and interprofessional collaboration.Ethics and disseminationEthics approval has been received from the following Human Research Ethics Committees: The University of Sydney (2018/926), The University of Queensland (2019000700/2018/926), University of Melbourne (1954239), Curtin University (HRE2019-0263) and Northern Sydney Local Health District (2019/ETH03632). Dissemination of findings will occur via peer-reviewed publications, conference presentations and social media.Trial registration numberACTRN12619000871145.