As delayed diagnosis and treatment of cerebrospinal fluid (CSF) leakage are common in current practice, this study was performed to determine associated factors and discuss appropriate strategies to deal with these problems. A retrospective analysis of all cases of CSF leakage in our hospital from 2007 to 2018, including 41 patients with CSF rhinorrhea and 5 with CSF otorhinorrhea, was performed. Symptoms, associated diseases, misdiagnoses, history of skull base repair surgical, previous medical costs, and number of hospital visits before visiting our institution were reviewed. The diagnoses, surgical reconstruction methods, and prognoses of the patients were analyzed. In 18 patients, CSF leakage was spontaneous, in 14 the cause was trauma, and in the remaining 14 the origin was iatrogenic. Twelve patients had been misdiagnosed with allergic rhinitis, rhinosinusitis, or otitis media. Twelve cases had intracranial infection and 14 suffered airway infection. Six had undergone unsuccessful craniotomy, endonasal endoscopic surgery, or ear surgery for treatment of CSF leakage before visiting our institute. This resulted in an average of 5.13 ± 1.32 referrals and medical costs of up to 20,795.7 ± 4553.80 RMB. The success rate was 97.83% after repairing CSF fistulae in our hospital. The septal floor flap (SFF) method (based on ethmoidal arteries) to treat CSF rhinorrhea showed a success rate of 100% in 12 patients. Therefore, early localization, clinical diagnosis, and appropriate repair surgery can avoid the occurrence of delayed events. Pedicled flaps, including SFF, are recommended to manage challenging CSF rhinorrhea.