Abstract Background Nonspecific discharge diagnoses after acute hospital courses represent patients discharged without an established cause of their complaints. These patients should have a low risk of adverse outcomes as serious conditions should have been ruled out. We aimed to investigate the mortality and readmissions following nonspecific discharge diagnoses compared to disease-specific diagnoses and assessed different nonspecific subgroups. Methods Register-based cohort study including hospital courses beginning in emergency departments across 3 regions of Denmark during March 2019–February 2020. We identified nonspecific diagnoses from the R- and Z03-chapter in the ICD-10 classification and excluded injuries, among others—remaining diagnoses were considered disease-specific. Outcomes were 30-day mortality and readmission, the groups were compared by Cox regression hazard ratios (HR), unadjusted and adjusted for socioeconomics, comorbidity, administrative information and laboratory results. We stratified into short (3–