IntroductionUpper quadrant musculoskeletal disorders (UQMD), comprising of cranial, cervical, shoulder and upper extremity disorders, are among the most frequently reported disorders in clinical practice. Thoracic high velocity low amplitude thrust (Tx-HVLAT) manipulation is a form of conservative management recommended in systematic reviews as an effective treatment option for aspects of UQMD disorders such headache, shoulder pain and lateral elbow pain. However, no recent systematic reviews have assessed the effectiveness across UQMD. Therefore, this systematic review aims to update the current evidence on the effectiveness of Tx-HVLAT for patients with UQMD on (1) patient-reported outcomes, (2) performance measures or (3) psychosocial outcomes.Methods and analysisThe Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, PEDro and Index to Chiropractic Literature will be searched from inception using Medical Subject Headings (MeSH), Thesaurus and/or free-text words. Combinations will be made based on localisation, disorder, intervention and design. Following guidelines as advised by the Cochrane Back Review Group, published randomised controlled trials will be included. Two review authors will independently assess the risk of bias (ROB) using the Cochrane Back Review Group’s recommended ROB2 tool and will independently extract the data using a standardised data extraction form. Overall quality of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. For continuous data, we will calculate standardised mean differences with 95% CIs. For dichotomous outcomes, relative risks and 95% CIs will be calculated. Where possible we will present a subgroup analysis by disorder. For pooling, a random-effects model will be used.Ethics and disseminationEthics approval is not required for this systematic review. The study findings will be submitted to a relevant peer-reviewed journal for dissemination and presented at relevant conferences.PROSPERO registration numberCRD42023429996.