Long-distance truck drivers (LDTDs) endure a disproportionately high burden of HIV in various global settings. However, unlike other most at-risk populations, the global burden of HIV among LDTDs has not been documented so far. The result has been poor allocation and distribution of the limited HIV preventive resources for LDTDs in most parts of the world. Thus, a systematic review and meta-analysis were conducted to assess the global burden of HIV among LDTDs. A comprehensive electronic search was conducted in PubMed, ProQuest Central, PubMed Central, CINAHL, and Global Index Medicus to identify relevant information published in English on HIV prevalence among LDTDs from 1989 to the 16thof May 2023. A random-effects meta-analysis was conducted to establish the burden of HIV at global and regional levels. The Joanna Briggs Institute (JBI) and Newcastle-Ottawa Scale (NOS) tools were used to assess the quality of the included studies.Of the 1787 articles identified, 43 were included. Most of the included studies were conducted in sub-Saharan Africa (44.19%, n=19), and Asia and the Pacific (37.21%, n=16). The pooled prevalence of HIV was 3.82%. The burden of HIV was highest in sub-Saharan Africa at 14.34%, followed by Asia and the Pacific at 2.14%, and lastly Western, Central Europe and North America at 0.17%. The overall heterogeneity score was (I2= 98.2%, p < 0.001).The global burden of HIV among LDTDs is 3.82%, six times higher than that of the general population globally. Compared to other regions, the burden of HIV is highest in sub-Saharan Africa at 14.34%, where it’s estimated to be 3% in the general population. Thus, LDTDs endure a disproportionately high burden of HIV compared to other populations. Consequently, more LDTD-centred HIV research and surveillance is needed at national and regional levels to institute tailored preventive policies and interventions.PROSPERO NumberCRD42023429390