The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan.This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted ≤7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess.After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance.Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem.