Aim To investigate whether elevated monocyte to lymphocyte ratio (MLR) is associated with the in-hospital mortality risk in elderly patients with acute myocardial infarction (AMI). Methods The medical history of 1 550 elderly patients with AMI hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Dalian Medical University from December 2015 to December 2021 was retrospectively collected, including 132 patients who died during hospitalization. It mainly includes gender, age, height, body weight, blood routine, lipid related indicators, fasting blood glucose (FBG), myocardial enzyme, type of myocardial infarction, estimated glomerular filtration rate (eGFR), in-hospital outcomes, prevalence of heart failure, diabetes, hypertension, and use of statins and antiplatelets during hospitalization. According to ROC curve analysis, patients with MLR＞0.342 were defined as high MLR group (n＝699), whereas patients with MLR≤0.342 were defined as low MLR group (n＝851). Results The age, white blood cell count, monocyte count, MLR, cardiac troponin I (cTnI), FBG, eGFR＜60 mL/(min·1.73 m²), male patients, heart failure, and proportion of all-cause deaths occurred during hospitalisation were higher in the high MLR group than those in the low MLR group (P＜0.05), body mass index (BMI), lymphocyte count, low density lipoprotein cholesterol (LDLC), eGFR＞60 mL/(min·1.73 m²), hypertension, and use of antiplatelet agents were lower in the high MLR group compared to the low MLR group (P＜0.05). Multivariate Logistic regression results showed that high MLR was independently associated with the in-hospital mortality risk in elderly AMI patients (OR＝1.812,95%CI:1.106～2.969,P＝0.018). The results of ROC curve analysis showed that the predictive ability of MLR combined with cTnI or FBG would be significantly improved, and the area under ROC curve was 0.789 and 0.739, respectively. Restrictive cubic spline (RCS) analysis results indicated a linear dose-response relationship between MLR and in-hospital outcomes in elderly AMI patients. Conclusion Elevated MLR is independently associated with the in-hospital mortality risk in elderly AMI patients, and clinicians can consider using MLR indicators in daily diagnosis for risk stratification and related treatment of such patients to improve their short-term prognosis.