Objective To explore the risk factors of multiple organ dysfunction syndrome (MODS) in elderly patients with heat stroke (HS) and develop a scoring system for predicting the occurrence of MODS in EHS patients. Methods We conducted a retrospective study of EHS patients, who were admitted to three hospitals in Chongqing from 2018 to 2023. According to their organ injury, all cases were divided into two groups: MODS group and non-MODS group. Various variables, including clinical characteristics and laboratory results were compared between the two groups. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors contributing to the progression of MODS in EHS patients. Additionally, ROC curves were employed to assess the sensitivity and specificity. Results A total of 167 HS patients were included in this study, of whom were beyond 60 years old. And 51 patients developed MODS. There were no significant differences in the age, gender, disease duration, mean arterial pressure, accompanying symptoms, HS type, neutrophil percentage, monocyte percentage, TT, Fib, TBIL, and DBIL (P>0.05) between the MODS and non-MODS groups. However, patients in the MODS group presented with significantly higher values in body temperature, heart rate, shock ratio, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, quick sepsis-related organ failure assessment (qSOFA) score, ICU admission rate, length of hospital stay, white blood cell count, neutrophil count, monocyte count, NLR, PT, APTT, CK, CKMB, myoglobin, ALT, and AST compared to the non-MODS group (P<0.05). Univariate Logistic regression analysis revealed that APACHE Ⅱ score, qSOFA score, white blood cell count, neutrophil count, GGT, ALT, AST, CK-MB, and LDH were risk factors of MODS development in the elderly HS patients (P<0.05). Furtherly, multivariate Logistic regression analysis indicated that qSOFA score and APACHE Ⅱ score were independent risk factors (P<0.05). Conclusion The EHS patients are susceptible to progressing to MODS, compared with long hospital stays and poor prognoses. The qSOFA score and APACHE Ⅱ score are effectively indicators for predicting the progression of MODS in EHS patients