Background The neutrophil-to-lymphocyte ratio (NLR) is positively associated with unfavorable outcomes in patients with cerebral infarction. This study aimed to investigate the relationship between the NLR and the short-term clinical outcome of acute pontine infarction. Methods Patients with acute pontine infarction were consecutively included. Clinical and laboratory data were collected. All patients were followed up at 3 months using modified Rankin Scale (mRS) scores. An unfavorable outcome was defined as an mRS score ≥ 3. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff values for patients with acute pontine infarction. risk factors can be predictive factors for an unfavorable outcome after acute pontine infarction. Results Two hundred fifty-six patients with acute pontine infarction were included in this study. The NLR was significantly higher in the unfavorable outcome group than in the favorable outcome group (P < 0.05). Additionally, the infarct size was significantly higher in the high NLR tertile group than in the low NLR tertile group (P < 0.05). Multivariate logistic regression analysis revealed that the baseline National Institutes of Health Stroke Scale (NIHSS) score, NLR, platelet count, and fasting blood glucose (FBG) level were significantly associated with unfavorable outcomes 3 months after acute pontine infarction. The optimal cutoff value of the NLR for predicting the 3-month outcome of acute pontine infarction was 3.055. The negative and positive predictive values of NLR were 85.7% and 61.3%, respectively, and the sensitivity and specificity of NLR were 69.2% and 80.9%. Conclusions We found that the NLR may be an independent predictive factor for the outcome of acute pontine infarction.