A better understanding of the risks and reasons for unplanned readmission is an essential component in reducing costs in the health care system and in optimizing patient safety and satisfaction. The reasons for unplanned readmission vary between different disciplines and procedures. The aim of this study was to identify reasons for readmission in view of different diagnoses in cranial neurosurgery. In this single-center retrospective study, adult patients after neurosurgical treatment were analyzed and grouped according to the indication based on International Classification of Diseases and Related Health Problems, Tenth Revision, German Modification diagnosis codes. The main outcome measure was unplanned readmission within 30 days of discharge. Further logistic regression models were performed to identify factors associated with unplanned rehospitalization. Of the 2474 patients analyzed, 183 underwent unplanned rehospitalization. Readmission rates differed between the diagnosis groups, with 9.19% in neoplasm, 8.26% in hydrocephalus, 5.76% in vascular, 6.13% after trauma, and 8.05% in the functional group. Several causes were considered to be preventable, such as wound healing disorders, seizures, or social reasons. Younger age, length of first stay, surgical treatment, and side diagnoses were predictors for unplanned readmission. Diagnoses with an increased risk of readmission were glioblastoma, traumatic subdural hematoma, or chronic subdural hematoma. Reasons and predictors for an unplanned readmission differ considerably among the index diagnosis groups. In addition to well-known reasons for readmission, we identified social indication, meaning a lack of home care, which is particularly prevalent in oncologic and elderly patients. A transitional care program could benefit these vulnerable patients.