Background and Aims Severe acute pancreatitis (SAP) with infected pancreatic necrosis (IPN) is a really challenging situation in clinical practice. A step-up, minimally invasive drainage or debridement is a widely accepted treatment approach. However, not all patients can benefit from a rigid implementation of step-up approach. In some patients, using a “skip-up” strategy based on step-up approach to perform a direct open debridement may provide a chance for treatment. Here, the authors summarized the treatment process of five patients with SAP complicated with IPN, so as to provide a reference for the selection of step-up or skip-up approaches.Methods The diagnosis and treatment process of five SAP patients with IPN was retrospectively analyzed, and the relevant literature was reviewed.Results Of the 5 patients, 3 cases were males and 2 cases were females, whose age ranged from 37 to 54 years, with an average age of (45.2±6.06) years. The length of hospital stay ranged from 22 to 108 d, with an average of (68±38.03) d. One patient was successfully cured after treatment by a step-up method, and two patients had a poor response after treatment with a step-up approach and eventually treatment was given up their families. Two patients achieved a better result after treatment using a skip-up strategy based on the step-up procedure.Conclusion Individualized treatment is critical for SAP patients complicated with IPN, striving for “one patient one plan”. A large proportion of patients can benefit from the treatment in a step-up approach. However, the rigid implementation of step-up approach must be avoided in patients presenting with fulminant organ failure, severe infection, and extensive abdominal abscesses, for whom a skip-up approach based on sufficient assessment may be more effective.