Objectives his study investigated the risk factors leading to serious suicide attempts with high medical severity. Methods Nine hundred and eighty-two patients who visited the emergency room after attempting suicide were divided into two groups: suicide attempters with high medical severity (25.3%) and those with low medical severity (74.7%). Demographic variables, clinical characteristics, and factors related to each suicide attempt were compared between the two groups. Multivariate logistic regression analysis was conducted to investigate risk factors for high medical severity in patients’ current suicide attempts. Results The results show that suicide attempters with high medical severity had more severe depression and psychological disturbances such as agitation, intense emotions, and self-reproach. Suicide attempters with high medical severity also had more serious risk factors for suicide such as repetitive/intense/continuous thoughts of suicide, suicidal planning, and a stronger wish to die. School/work problems and physical illnesses were related to high medical severity with more lethal methods. Logistic regression demonstrated that school/work problems, total risk rating, severity of suicidal ideation, and agitation were risks for more serious suicide attempts, whereas more frequent lifetime suicide attempts were a protective factor. Conclusion This study demonstrates that suicide attempters with high medical severity had more severe psychopathologies and risk factors related to suicidal behavior than those with low medical severity.