Background: Previous studies suggest an association between short-term exposure to carbon monoxide and my ocardial infarction. We performed a systematic review and meta-analysis to assess current evidence on this association to support the update of the World Health Organization (WHO) Global Air Quality Guidelines. Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials to update the evidence published in a previous systematic review up to 30th September 2018 for studies investigating the association between short-term exposure to ambient carbon monoxide (up to lag of seven days) and emergency department visits or hospital admissions and mortality due to myocardial infarction. Two reviewers assessed potentially eligible studies and performed data extraction independently. Random-effects meta-analysis was used to derive the pooled risk estimate per 1 mg/m3 increase in ambient carbon monoxide concentration. Risk of bias in individual studies was assessed using a domain-based assessment tool. The overall certainty of the body of evidence was evaluated using an adapted certainty of evidence assessment framework. Results: We evaluated 1,038 articles from the previous review and our updated literature search, of which, 26 satisfied our inclusion criteria. Overall, myocardial infarction was associated with exposure to ambient carbon monoxide concentration (risk ratio of 1.052, 95% confidence interval 1.017–1.089 per 1 mg/m3 increase). A third of studies were assessed to be at high risk of bias (RoB) due to inadequate adjustment for confounding. Using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, the overall evidence was assessed to be of moderate certainty. Conclusions: This review demonstrated that the pooled risk ratio for myocardial infarction was 1.052 (95% CI 1.017–1.089) per 1 mg/m3 increase in ambient carbon monoxide concentration. However, very few studies originated from low- and middle-income countries.