Background: The chest pain is a very common complaint among patients with acute coronary syndrome (ACS). The local thermotherapy can reduce or relieve the heart pain by suppressing metabolites as pain mediators. Objectives: This study aimed to determine the effect of local thermotherapy on the chest pain in patients with ACS. Methods: This clinical trial was conducted on 78 patients with ACS hospitalized in the ICU of Golestan Hospital of Ahvaz in 2016. Based on the sample size and inclusion criteria, and by a convenience sampling, the eligible patients were enrolled and randomized into two equal-sized groups, namely control and intervention, each containing 39 participants. During the local thermotherapy sessions, the patients received local heat by using a hot pack warmed to 50°C for five days. The control group only received the routine treatment. Data collection instruments included a demographic questionnaire and the Numerical Rating Scale (NRS). The NRS was completed by the participants before the intervention and five days after it. Data were analyzed using the descriptive tests, correlation coefficient, independent t-test, Chi-square, and logistic regression in SPSS 20. Results: The mean pain severity in the case group before the intervention was 3.22 ± 0.86 and after the intervention, it decreased to 2.61 ± 0.7, indicating the effect of local thermotherapy. However, it was not statistically significant (P > 0.05). There was no significant relationship between age, gender, diabetes, hypertension, and hyperlipidemia, and the pain severity in this study (P > 0.05). Logistic regression analysis showed that women experienced more pain than men did. Conclusions: This study suggested the slight effectiveness of local thermotherapy in reducing the severity of pain in these patients. As a result, further studies are recommended.