AIMS: Secondary sclerosing cholangitis (SSC) is a rare progressive biliary disease. We aimed to analyze the underlying causes, treatment approaches, and prognosis of SSC in order to enhance awareness of this disease. METHODS: A retrospective analysis was conducted on patients diagnosed with SSC in a single tertiary center in China between October 2016 and March 2024, focusing on the etiology, treatment modalities, and follow-up outcomes. Clinical outcomes were compared to patients with primary sclerosing cholangitis during the same period. RESULTS: A total of 21 patients were included in the study, with a median age of 42 (interquartile range 34, 57). The primary causes of SSC included surgical injury (seven cases, 33.3%) and drug-induction (six cases, 28.6%). Eight patients (38.1%) underwent ERCP, six patients (28.6%) received PTCD, and two patients (9.5%) underwent choledochoscopic bile duct dilation or stone extraction.Median follow-up time was 13 (interquartile range 10, 35) months, during which five patients (23.8%) died and five patients (23.8%) underwent liver transplants.Comparison of patients who received biliary decompression interventions and patients who did not revealed no significant difference in prognosis ( CONCLUSIONS: SSC is a complex disease with varied etiologies and poor prognosis, particularly when caused by bile duct surgical trauma. Bile duct decompression like ERCP does not offer long-term survival benefits. SSC exhibited a trend towards a less favorable prognosis compared to PSC.