Background: There are approximately two billion workers in the informal economy globally. Compared to workers in the formal economy, these workers are often marginalised with minimal or no benefits from occupational health and safety regulations, labour laws, social protection and/or health care. Thus, informal economy workers may have higher occupational health risks compared to their formal counterparts. Our objective was to systematically review and meta-analyse evidence on relative differences (or inequalities) in health services use and health outcomes among informal economy workers, compared with formal economy workers. Methods: We searched PubMed and EMBASE in March 2020 for studies published in 1999–2020. The eligible population was informal economy workers. The comparator was formal economy workers. The eligible outcomes were general and occupational health services use, fatal and non-fatal occupational injuries, HIV, tuberculosis, musculoskeletal disorders, depression, noise-induced hearing loss and respiratory infections. Two authors independently screened records, extracted data, assessed risk of bias with RoB-SPEO, and assessed quality of evidence with GRADE. Inverse variance meta-analyses were conducted with random effects. Results: Twelve studies with 1,637,297 participants from seven countries in four WHO regions (Africa, Americas, Eastern Mediterranean and Western Pacific) were included. Compared with formal economy workers, informal economy workers were found to be less likely to use any health services (odds ratio 0.89, 95% confidence interval 0.85–0.94, four studies, 195,667 participants, I2 89%, low quality of evidence) and more likely to have depression (odds ratio 5.02, 95% confidence interval 2.72–9.27, three studies, 26,260 participants, I2 87%, low quality of evidence). We are very uncertain about the other outcomes (very-low quality of evidence). Conclusion: Informal economy workers may be less likely than formal economy workers to use any health services and more likely to have depression. The evidence is uncertain for relative differences in the other eligible outcomes. Further research is warranted to strengthen the current body of evidence and needed to improve population health and reduce health inequalities among workers.