Objectives This umbrella review aims to summarise the evidence about electronic nicotine delivery systems’ (ENDS) risk and safety health profile to inform ENDS health communication strategies.

Data sources and study selection Six databases were searched for systematic reviews presenting evidence on ENDS-related health effects. Ninety reviews divided into five categories were included: toxicity=20, health effects=40, role in smoking cessation=24, role in transition to combustible cigarettes (CCs)=13 and industry marketing claims=4.

Data extraction Findings were synthesised in narrative summaries. Meta-analyses were conducted by study type when appropriate. Quality assessment was conducted using the Measurement Tool to Assess Systematic Reviews. The Institute of Medicine’s Levels of Evidence Framework was used to classify the evidence into high-level, moderate, limited-suggestive and limited-not-conclusive.

Data synthesis We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes serious injuries due to explosion or poisoning; increases smoking cessation in clinical trials but not in observational studies; increases CC initiation; and exposure to ENDS marketing increases its use/intention to use. Evidence was moderate for ENDS association with mental health and substance use, limited-suggestive for cardiovascular, and limited-not-conclusive for cancer, ear, ocular and oral diseases, and pregnancy outcomes.

Conclusions As evidence is accumulating, ENDS communication can focus on high-level evidence on ENDS association with toxicity, nicotine addiction, respiratory disease, ENDS-specific harm (explosion, poisoning) and anti-ENDS industry sentiment. Direct comparison between the harm of CCs and ENDS should be avoided.

PROSPERO registration number CRD42021241630.