Simple SummaryDirofilariasis is caused byDirofilariaspp. worm infections, transmitted by mosquitoes, and affects humans and animals worldwide. Often, infected animals show symptoms relating to the cardiopulmonary system (heart and lung) and subcutaneous tissue (eye and skin). This study assessed the current published data on the distribution and prevalence of dirofilariasis across Sri Lanka and India. This analysis found that almost all cases of human dirofilariasis reported in Sri Lanka and India are presented as subcutaneous infections, with the eye being the most commonly affected organ. Both heartworm and subcutaneous infections are found in the dog populations in India. However, only subcutaneous infections have so far been reported in Sri Lanka, and the rationale behind this geographical distribution of infection patterns of dirofilariasis remains unknown and warrants further research. There was a low infection rate in the pet and working dog populations in India and Sri Lanka, but this may change due to climate change and emerging anti-parasitic drug resistance. It was identified in this study that some regions within India and Sri Lanka have not yet been surveyed for dirofilariasis, and future studies need to target these unsurveyed areas to better understand the geographical and species distribution of dirofilariasis in these two countries.AbstractDirofilariasis is an emerging vector-borne tropical disease of public health importance that mainly affects humans and dogs.Dirofilaria immitisandD. repensare the two well-documented dirofilariasis-causing filarioid helminths of both medical and veterinary concerns in India and Sri Lanka. This systematic review and meta-analysis aimed to describe and summarize the current evidence of dirofilariasis prevalence and distribution in India and Sri Lanka. Interestingly,D. repensis reported to circulate in both dogs (prevalence of 35.8% (95% CI: 11.23–60.69)) and humans (97% of published case reports) in India and Sri Lanka, butD. immitisis reported to be present in the dog populations in India (prevalence of 9.7% (95% CI: 8.5–11.0%)), and so far, it has not been reported in Sri Lanka. This peculiar distribution ofD. immitisandD. repensin the two neighbouring countries could be due to the interaction between the two parasite species, which could affect the pattern of infection of the two worm species in dogs and thus influence the geographical distribution of these two filarial worms. In medical and veterinary practice, histopathology was the most commonly used diagnostic technique (31.3%; 95% CI 2.5–60.2%). The low specificity of histopathology to speciate the variousDirofilariaspp. may lead to misdiagnosis. It was identified in this study that several regions of India and Sri Lanka have not yet been surveyed for dirofilariasis. This limits our understanding of the geographical distribution and interspecies interactions of the two parasites within these countries. Parasite distribution, disease prevalence, and interspecies interactions between the vectors and the host should be targeted for future research.