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<h2>Abstract</h2><h3>Background</h3> Suicide is a serious public health problem worldwide, and South Korea has one of the highest suicide rates among OECD countries. This study aimed to compare and analyze the case fatality rates (CFRs) and incidence of suicide attempts according to the method used, using a nationwide emergency department (ED) database. <h3>Methods</h3> This retrospective multicenter observational study was conducted using data from the National Emergency Department Information System (NEDIS) database from January 2014 to December 2019. All patients with suicide attempts or intentional self-harm who visited level 1 or 2 EDs were included. The primary outcome was in-hospital mortality and the secondary outcome was the incidence of suicide attempts. CFRs and age- and sex-standardized incidence rates were calculated for each suicide method. <h3>Results</h3> A total of 176,771 patients were included in the analysis. The most common suicide methods were poisoning (57.8 %), sharp/blunt objects (27.5 %) and hanging (7.1 %). Hanging/suffocation had the highest CFR (50.1 %), followed by jumping from a height (33.2 %) and drowning (16.2 %). The adjusted odds ratios for in-hospital mortality were 31.4 (95 % CI: 29.8–33.1) for hanging/suffocation, 20.0 (95 % CI: 18.6–21.6) for jumping from a height, and 6.96 (95 % CI: 6.10–7.95) for drowning, compared to poisoning. The age- and sex-standardized incidence of suicide attempts increased from 52.5 to 70.2 cases per 100,000 person-years from 2014 to 2019, whereas the CFRs for each method showed a decreasing trend. <h3>Conclusion</h3> CFRs and incidence rates of suicide attempts varied significantly according to the method used. Hanging/suffocation was the most lethal, while poisoning and sharp/blunt objects accounted for the majority of attempts. These findings underscore the importance of suicide prevention policies that incorporate means restriction strategies, such as limiting access to high-lethality or high-incidence methods, and enforcing safer medication regulations. Additionally, ED-based interventions, including post-attempt counseling and public awareness programs, could play a vital role in reducing future suicide risk.