OBJECTIVES: The purpose of this study was to systematically summarise the empirical evidence on the prevalence of HIV among long-distance truck drivers (LDTDs) from all parts of the world. DESIGN: A systematic review and meta-analysis were conducted. DATA SOURCES: We searched PubMed, ProQuest Central, PubMed Central, Cumulated Index to Nursing and Allied Health Literature and Global Index Medicus to identify relevant information published from 1989 to 16 May 2023. ELIGIBILITY CRITERIA: Peer-reviewed publications of English language reporting on the prevalence of HIV among LDTDs were included. Non-empirical studies like literature reviews were excluded. DATA EXTRACTION AND SYNTHESIS: Using a standardised data abstraction form, we extracted information on study characteristics and HIV prevalence levels. Crude prevalence estimates per 100 participants were computed and later transformed using logit transformation to have them follow a normal distribution. A meta-analysis of prevalences using the random effects model was performed. The I statistic was used to quantify the degree of heterogeneity across studies. A subgroup analysis using meta-regression was performed to investigate factors that could explain variability across studies. The Joanna Briggs Institute tools and Newcastle-Ottawa Scale were used to assess the quality of the included studies. To assess the certainty of evidence, the Grading of Recommendations Assessment, Development, and Evaluation approach was used. RESULTS: Of the 1787 articles identified, 42 were included. Most of the included studies were conducted in sub-Saharan Africa (45.23%, n=19) and Asia and the Pacific (35.71%, n=15). The pooled prevalence of HIV was 3.86%, 95% CI (2.22% to 6.64%). The burden of HIV was highest in sub-Saharan Africa at 14.34%, 95% CI (9.94% to 20.26%), followed by Asia and the Pacific at 2.12%, 95 CI (0.94% to 4.7%) and lastly Western, Central Europe and North America at 0.17%, 95% CI (0.03% to 0.82%). The overall heterogeneity score was (I=98.2%, p<0.001). CONCLUSION: The global burden of HIV among LDTDs is 3.86%, six times higher than that of the general population globally. Compared with other regions, the burden of HIV is highest in sub-Saharan Africa at 14.34%, where it is estimated to be 3% in the general population. Thus, LDTDs endure a disproportionately high burden of HIV compared with 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 REGISTRATION NUMBER: CRD42023429390.