Purpose: Most bee sting injuries are benign, although sometimes they can result in life threatening outcomes, such as anaphylaxis and death. The purpose of this study was to investigate the epidemiologic status of bee sting injuries in Korea and to identify risk factors associated with severe systemic reactions (SSRs). Materials and Methods: Cases were extracted from a multicenter retrospective registry for patients who had visited emergency departments (EDs) for bee sting injuries. SSRs were defined as hypotension or altered mental status upon ED arrival, hospitalization, or death. Patient demographics and injury characteristics were compared between SSR and non-SSR groups. Logistic regression was performed to identify risk factors for bee sting-associated SSRs, and the characteristics of fatality cases were summarized. Results: Among the 9673 patients with bee sting injuries, 537 had an SSR and 38 died. The most frequent injury sites included the hands and head/face. Logistic regression analysis revealed that the occurrence of SSRs was associated with male sex [odds ratio (95% confidence interval); 1.634 (1.133–2.357)] and age [1.030 (1.020–1.041)]. Additionally, the risk of SSRs from trunk and head/ face stings was high [2.858 (1.405–5.815) and 2.123 (1.333–3.382), respectively]. Bee venom acupuncture [3.685 (1.408–9.641)] and stings in the winter [4.573 (1.420–14.723)] were factors that increased the risk of SSRs. Conclusion Our findings emphasize the need for implementing safety policies and education on bee sting-related incidents to protect high-risk groups.