Prompt diagnosis and timely treatment are important for reducing morbidity and mortality from pyogenic liver abscess (PLA). The purpose of this study was to investigate the importance of the delta neutrophil index (DNI) reflecting the fraction of immature granulocytes as a predictor of the development of in-hospital hypotension in initially stable patients with PLA. We retrospectively identified 308 consecutive patients (>18 years) who were hemodynamically stable at presentation and diagnosed with PLA in the emergency department (ED) between January 2011 and September 2017. The outcome of interest was in-hospital hypotension 1-24 hours after admission to the ED. A high DNI at ED admission was an independent predictor of the development of in-hospital hypotension in initially stable patients with PLA (odds ratio [OR]: 1.44, 95.0% confidence interval [CI]: 1.06-1.95; P = 0.02). A DNI > 3.3% was associated with in-hospital hypotension at ED admission (OR: 5.37, 95.0% CI: 2.91-9.92; P < 0.001). The development of in-hospital hypotension was associated with an increased risk of 30-day mortality (HR: 8.55, 95.0% CI: 2.57-28.4; P < 0.001). A high DNI independently predicts the development of in-hospital hypotension in initially stable patients with PLA. In-hospital hypotension is associated with an increased risk of 30-day mortality.