Objective: The chest compression depth recommended in the current guidelines for average adult cardiopulmonary resuscitation is approximately 1/4-1/5 depth of the external chest anteroposterior (AP) diameter and at least 50 mm but less than 60 mm. The purpose of this study was to determine the proper compression depth in patients with amyotrophic lateral sclerosis (ALS). Methods: A retrospective analysis of the chest computed tomography scans obtained between January 2014 and December 2018 was performed, and the chest anatomical parameters, such as external, internal chest, and heart AP diameters, were measured. The primary outcomes were a 1/4 and 1/5 depth of an external chest AP diameter. Based on the values of these parameters, the heart compression fractures (HCF) and over compression depth (OCD) from 40 to 60 mm depths with every 5 mm interval were calculated. All outcomes in the two groups were compared. Results: Ninety three of 108 ALS and 93 of 17,150 healthy individuals were selected randomly from a database and analyzed. The mean±standard deviations of 1/4 and 1/5 depth of the external chest AP diameter in ALS were significantly lower than in healthy individuals (48.57±4.60 mm vs. 53.43±4.93 mm, 38.86±3.68 mm vs. 42.75±3.94 mm, respectively, all P<0.001). The HCF values were similar in the two groups. The number of OCD with 55 and 60 mm in the ALS group were increased (all P<0.05, univariate analysis) Conclusion An approximately 50 mm depth of chest compression could be appropriate, but an excessive depth greater than 55 mm is more likely to cause complications for ALS patients.