Background and aim: Open surgery is a traditional method for treating severe acute pancreatitis (SAP), but it has greater trauma to the patient's body, so the incidence of postoperative complications is high. This study aimed to investigate the efficacy of ultrasound-guided percutaneous catheter drainage (PCD) in the treatment of SAP complicated with necrosis and infection. Methods: Eighty patients with SAP complicated with necrosis and infection were enrolled in this study. According to the treatment method, patients were divided into the control group (42 cases) and the observation group (38 cases), which received open abdominal drainage and ultrasound-guided PCD, respectively. Treatment efficacy, laboratory indicators, inflammatory indexes, drainage liquid bacteria culture, hospitalization time, reoperation and death/abandonment in two groups were measured and compared. Results: After treatment the blood WBC, blood amylase, urinary amylase, blood glucose levels, serum procalcitonin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 levels in the observation group were significantly lower than those in the control group, respectively (P < 0.05), and the hospitalization time and death/abandonment rate in the observation group were significantly lower than those in the control group, respectively (P < 0.05). There was no significant difference between the effective rate of treatment or the bacterial culture result between the two groups (P > 0.05). Conclusion: Ultrasound-guided PCD is an effective and safe method for treatment of SAP complicated with necrosis and infection. It is worthy of clinical application.