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Introduction The lumbar puncture (LP) technique is widely used for diagnostic and therapeutic purposes. In recent years, the paramedian approach technique (PAT) has gained increasing interest due to its advantages over the conventional midline approach technique (MAT) that has been traditionally employed in clinical practice for LP. However, there have been inconsistent discussions regarding the efficacy of different LP techniques. Based on digital virtual human and computer simulation techniques, a new approach called computerised modified PAT (CMPAT) was proposed. Therefore, the aim of this study is to discuss a randomised controlled trial (RCT) protocol to investigate and compare the effects of CMPAT and MAT in patients undergoing LP.Methods and analysis We will conduct a prospective, multicentre RCT. The study will recruit 84 patients aged 18–99 years who require LP. Participants will be randomly assigned to either the CMPAT treatment group (group A) or the MAT treatment group (group B). The primary outcome measure will be the number of needle insertion attempts required for a successful LP. Secondary outcomes will include the puncture success rate, pain assessment in the back, head, and legs, and the occurrence of complications. The measurement of these secondary outcomes will be taken during the procedure, as well as at specific time points: 30 min, 6 hours, 1 day, 3 days, 7 days, 2 weeks and 4 weeks after the procedure. Pain levels will be assessed using a Numerical Rating Scale.Ethics and dissemination Ethical approval (2022YF052-01) has been obtained from the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China. The research findings will be published in an international peer-reviewed scientific journal and presented at scientific conferences.Trial registration number ChiCTR2300067937.