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Objective: The aim of this study was to assess the association between the presence of a right-to-left shunt (RLS) and neurological decompression sickness (NDCS) and asymptomatic brain lesions among otherwise healthy divers. Background: Next to drowning, NDCS is the most severe phenotype of diving-related disease and may cause permanent damage to the brain and spinal cord. Several observational reports have described the presence of an RLS as a significant risk factor for neurological complications in divers, ranging from asymptomatic brain lesions to NDCS. Methods: We systematically reviewed the MEDLINE, Embase, and CENTRAL databases from inception until November 2021. A random-effects model was used to compute odds ratios. Results: Nine observational studies consisting of 1830 divers (neurological DCS: 954; healthy divers: 876) were included. RLS was significantly more prevalent in divers with NDCS compared to those without (62.6% vs. 27.3%; odds ratio (OR): 3.83; 95% CI: 2.79–5.27). Regarding RLS size, high-grade RLS was more prevalent in the NDCS group than the no NDCS group (57.8% versus 18.4%; OR: 4.98; 95% CI: 2.86–8.67). Further subgroup analysis revealed a stronger association with the inner ear (OR: 12.13; 95% CI: 8.10–18.17) compared to cerebral (OR: 4.96; 95% CI: 2.43–10.12) and spinal cord (OR: 2.47; 95% CI: 2.74–7.42) DCS. RLS was more prevalent in divers with asymptomatic ischemic brain lesions than those without any lesions (46.0% vs. 38.0%); however, this was not statistically significant (OR: 1.53; 95% CI: 0.80–2.91). Conclusions: RLS, particularly high-grade RLS, is associated with greater risk of NDCS. No statistically significant association between RLS and asymptomatic brain lesions was found.