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Abstract Background Cardiovascular disease is the leading cause of death worldwide, with significantly worse mortality-related outcomes in ethnic minorities in developed countries. A systematic literature review and meta-analysis of observational studies was conducted to investigate cardiovascular disease-related mortality inequalities between South Asian and White Caucasian ethnic groups. Methods Published studies on mortality between South Asians and Whites in developed countries were retrieved from MEDLINE, PubMed, Embase, Web of Science, and grey literature sources (inception—April 2021) and critically appraised using the Quality in Prognosis Studies tool. Bayesian random-effects meta-analyses were performed for both primary and secondary outcomes. Heterogeneity was determined using the I 2 statistic. Results Of the 9879 studies screened originally, 41 were deemed eligible. A further 3 studies were included via the later search. Of these, 15 reported cardiovascular disease-related mortality, 23 reported all-cause mortality, and 6 reported both. The meta-analysis results showed that South Asians had a significantly increased risk of cardiovascular disease mortality compared to Whites (risk ratio = 1.32; 95% credible interval = 1.14 to 1.54) and a decreased risk of all-cause mortality (risk ratio = 0.95; 95% credible interval = 0.83 to 1.12). Discussion South Asians had statistically significantly higher odds of cardiovascular disease-related mortality compared to Whites, but not for all-cause mortality. Risk of bias was a serious concern mainly due to a lack of confounders being reported. Systematic review registration PROSPERO: CRD42021240865
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