BACKGROUND To assess the prevalence, risk factors, clinical characteristics, and outcomes of acute pancreatitis (AP) in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS All patients diagnosed with HFRS admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to July 2020 were enrolled. Patients with and without AP were compared by two risk stratification models: (1) a multivariate regression analysis using propensity score to adjust for confounding and (2) a propensity-matched nested case-control study. RESULTS A total of 346 patients were enrolled in the cohort study, 29 of whom (8.4%) were diagnosed as AP. There was no significant difference between patients with and without AP with regards to common risk factors and presenting signs/symptoms other than gastrointestinal symptoms (p < 0.01). The patients with AP had a significantly higher 90-day mortality rate (24.1% vs. 3.5%, OR 8.9, 95% CI 1.3 to 103.4, p = 0.045), and significantly shorter duration of therapy free-days to 28 day such as RRT and mechanical ventilation free days (p < 0.05, respectively). CONCLUSIONS Our study indicated that AP was independently associated with higher mortality in HFRS patients. While considering the difficulty of early recognition of AP among HFRS patients with similar signs and/or symptoms, further laboratory and imaging studies might help identify these patients at risk of poor clinical prognosis.