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Policy PointsIncome is thought to impact a broad range of health outcomes. However, whether income inequality (how unequal the distribution of income is in a population) has an additional impact on health is extensively debated.Studies that use multilevel data, which have recently increased in popularity, are necessary to separate the contextual effects of income inequality on health from the effects of individual income on health.Our systematic review found only small associations between income inequality and poor self‐rated health and all‐cause mortality. The available evidence does not suggest causality, although it remains methodologically flawed and limited, with very few studies using natural experimental approaches or examining income inequality at the national level. Context: Whether income inequality has a direct effect on health or is only associated because of the effect of individual income has long been debated. We aimed to understand the association between income inequality and self‐rated health (SRH) and all‐cause mortality (mortality) and assess if these relationships are likely to be causal. Methods: We searched Medline, ISI Web of Science, Embase, and EconLit (PROSPERO: CRD42021252791) for studies considering income inequality and SRH or mortality using multilevel data and adjusting for individual‐level socioeconomic position. We calculated pooled odds ratios (ORs) for poor SRH and relative risk ratios (RRs) for mortality from random‐effects meta‐analyses. We critically appraised included studies using the Risk of Bias in Nonrandomized Studies – of Interventions tool. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework and causality using Bradford Hill (BH) viewpoints. Findings: The primary meta‐analyses included 2,916,576 participants in 38 cross‐sectional studies assessing SRH and 10,727,470 participants in 14 cohort studies of mortality. Per 0.05‐unit increase in the Gini coefficient, a measure of income inequality, the ORs and RRs (95% confidence intervals) for SRH and mortality were 1.06 (1.03‐1.08) and 1.02 (1.00‐1.04), respectively. A total of 63.2% of SRH and 50.0% of mortality studies were at serious risk of bias (RoB), resulting in very low and low certainty ratings, respectively. For SRH and mortality, we did not identify relevant evidence to assess the specificity or, for SRH only, the experiment BH viewpoints; evidence for strength of association and dose–response gradient was inconclusive because of the high RoB; we found evidence in support of temporality and plausibility. Conclusions: Increased income inequality is only marginally associated with SRH and mortality, but the current evidence base is too methodologically limited to support a causal relationship. To address the gaps we identified, future research should focus on income inequality measured at the national level and addressing confounding with natural experiment approaches. [ABSTRACT FROM AUTHOR]