Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. We investigated whether the monocyte to high-density lipoprotein ratio (MHR) is related to HT. Consecutive patients with ischemic stroke within 24 h of symptom onset were included in this study. HT was diagnosed by follow-up brain imaging after admission, and was classified as asymptomatic or symptomatic according to whether patients showed any neurologic worsening. Logistic regression was performed to estimate the association between MHR and HT. Of the 974 enrolled patients, 148 (15.2%) developed HT, and 24 (2.5%) patients experienced symptomatic HT. Compared to the highest MHR tertile (> 0.37), the lowest MHR tertile (< 0.22) was associated with 1.81-fold increase (95% CI 1.08-3.01, P = 0.024) in the odds of HT and 3.82-fold increase (95% CI 1.04-14.00, P = 0.043) in the odds of symptomatic HT after adjustment for possible confounders. Using a multivariate logistic regression model with restricted cubic spline, we found that elevated MHR was associated with a decreased risk of HT and symptomatic HT. In summary, lower MHR was independently associated with increased risk of HT and symptomatic HT in patients with ischemic stroke.