Although randomized controlled trials (RCTs) are generally seen as providing more certainty about the evidence of an effect, many interventions in infectious diseases are examined in observational studies. These include rare cases of treatment that cannot be examined in a RCT (e.g. appropriate vs. inappropriate empirical antibiotic treatment) [1,2], complex interventions that are difficult to examine in RCTs (e.g. infection control or antibiotic stewardship) [3,4], comparative effective research and quality improvement programmes (comparisons between commonly used, approved, antibiotics, monotherapy vs. combinations or treatment durations) for which resources for RCTs are lacking [5e10], or studies rapidly launched during outbreaks, such as the coronavirus disease 2019 (COVID-19) pandemic [11e13]. Summarizing these in systematic reviews is appealing; however, systematic reviews of observational studies suffer from the same shortcomings as primary observational studies when causal inferences need to be made. Consistent errors in observational studies may even be magnified by narrowing the confidence intervals through meta-analysis.In this editorial note, we provide our recommendations and expectations for systematic reviews and meta-analyses of observational studies examining an exposure or intervention. Guidance on performance and reporting of such studies has been published, and we recommend following these [14,15]. We explain the specific pitfalls of such studies and what we require from authors of systematic reviews of observational studies.