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Context: Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use. Objective: To evaluate the reported adverse effects of energy drink consumption. Data Sources: The electronic databases MEDLINE, EMBASE, and PubMed were searched for relevant studies from inception to November 2019, and pertinent data were abstracted. Study Selection: Only clinical studies reporting adverse events after energy drink consumption were included. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Data regarding sample size characteristics, energy drink characteristics, comparators, and all adverse events were extracted in duplicate and recorded. Results: A total of 32 studies and 96,549 individuals were included. Frequently reported adverse events in the pediatric population were insomnia (35.4%), stress (35.4%), and depressive mood (23.1%). Frequently reported adverse events in the adult population were insomnia (24.7%), jitteriness/restlessness/shaking hands (29.8%), and gastrointestinal upset (21.6%). Alcohol mixed with energy drinks significantly reduced the likelihood of sedation effects but increased the likelihood of stimulatory effects. Energy drink consumption significantly increased the odds of insomnia (OR, 5.02; 95% CI, 1.72-14.63) and jitteriness/activeness (OR, 3.52; 95% CI, 1.28-9.67) compared with the control group. Conclusion: The authors recommend that individuals avoid frequent energy drink consumption (5-7 energy drinks/week) and avoid co-consumption with alcohol; increased regulatory standards should be placed in the sale of energy drinks, particularly with regard to the pediatric population.