Abstract Background Hepatosplenic schistosomiasis (HSS) is an important chronic complication of Schistosoma infection. However, its diagnosis and management are complicated due to lack of evidence and uniform guidance. In this study, we described the clinical profile and management of HSS in one of Ethiopia's referral hospitals. Methods A hospital-based, cross-sectional study was conducted using the medical records of patients diagnosed with HSS based on clinical symptoms and typical ultrasound findings observed at the gastroenterology clinic of Dessie referral hospital from September 2018 to December 2019. Results A total of 55 patient files were evaluated. Most patients (n=39; 70%) presented with upper gastrointestinal bleeding and severe anaemia. Nearly three-quarters of patients were admitted and 31 (56%) received a blood transfusion. Hepatitis B coinfection was documented in 11 patients (20%). Upper gastrointestinal endoscopy was performed in 31 patients (56%), in whom large oesophageal varices with red signs were the most common finding. Among patients who had endoscopy, band ligation was carried out in 21 cases (68%). Praziquantel was administered to 11 patients (20%). Conclusion HSS causes severe complications of portal hypertension, like variceal bleeding, which are currently not adequately treated. In addition to already existing preventive efforts, we advise control programmes to also address acute management and rehabilitation of these patients.