To evaluate the influence factors of different compression modes on restoration of spontaneous circulation (ROSC) and outcomes in patients with cardiac arrest. Based on the national database of emergency cardiac arrest treatment, the clinical data of 517 patients with cardiac arrest admitted to 14 teaching hospitals in 7 provinces from July 2015 to July 2017 were enrolled. According to the way of compression, the patients were divided into mechanical compression group and hands-only compression group. The demographic data, resuscitation parameters [compression frequency, monitored ventilation frequency, duration of resuscitation, drug usage] and physiological parameters [end-expiratory partial pressure of carbon dioxide (PETCO2), pulse oxygen saturation (SpO2)] were collected. The ROSC rates and 24-hour, 7-day, 28-day survival rates were compared between the two groups. Multivariate Logistic regression model was used to analyze the influencing factors of ROSC according to whether the duration of resuscitation was longer than 60 minutes. Of 517 patients, 24 were excluded because of incomplete data. A total of 493 patients were enrolled in the analysis with 214 patients in the mechanical compression group, and 279 in the hands-only compression group. Compared with hands-only compression group, the patients in mechanical compression group had higher age, proportion of chronic obstructive pulmonary disease (COPD) and PETCO2, fewer un-shockable rhythm, less compression rate, more epinephrine and sodium bicarbonate usage, and longer duration of cardiopulmonary resuscitation (CPR). Although the rate of ROSC in the mechanical compression group was higher than that in the hands-only compression group [36.9% (79/214) vs. 30.5% (85/279)], there was no significant difference in the rate of ROSC between the two groups [odds ratio (OR) = 1.10, 95% confidence interval (95%CI) = 0.68-1.76, P = 0.693], even after adjusted for con-variables by multivariate Logistic regression (OR = 1.21, 95%CI = 0.54-1.88, P = 0.054). Furthermore, 24-hour, 7-day, and 28-day survival rate also showed no significant difference in both univariate model and multivariate model. Comparisons of resuscitation parameters and physiological parameters between the two groups showed that when the duration of CPR < 60 minutes, the pressing frequency of the mechanical compression group was lower, ventilation frequency and adrenaline dosage were higher; and when the duration of CPR ≥ 60 minutes, the adrenaline dosage and PETCO2 of the mechanical compression group were higher. Multivariate Logistic regression analysis showed that among patients with a duration of CPR < 60 minutes, un-shockable rhythm (OR = 0.29, 95%CI = 0.05-0.75, P = 0.015), compression rate > 120 times/min (OR = 0.39, 95%CI = 0.24-0.64, P < 0.001), ventilation frequency > 40 times/min (OR = 0.50, 95%CI = 0.31-0.84, P = 0.034) were independent risk factors for ROSC; while PETCO2 ≥ 20 mmHg (1 mmHg = 0.133 kPa) was protective factor for ROSC (OR = 2.79, 95%CI = 1.88-4.49, P < 0.001). However, for patients with CPR duration ≥ 60 minutes, ≥ 65 years old (OR = 0.33, 95%CI = 0.15-0.67, P = 0.018), admission at night (OR = 0.74, 95%CI = 0.59-0.94, P = 0.035), un-shockable rhythm (OR = 0.38, 95%CI = 0.25-0.65, P = 0.001), non-cardiogenic cardiac arrest (OR = 0.35, 95%CI = 0.25-0.48, P = 0.013), previous history of diabetes mellitus (OR = 0.46, 95%CI = 0.27-0.82, P = 0.015) were independent risk factors for ROSC, and cardiac arrest occurred in emergency room (OR = 2.02, 95%CI = 1.02-2.92, P = 0.023), mechanical compression (OR = 1.41, 95%CI = 1.12-1.75, P = 0.043), PETCO2 ≥ 20 mmHg (OR = 2.94, 95%CI = 1.34-4.54, P = 0.012), previous history of acute coronary syndrome (ACS; OR = 2.47, 95%CI = 1.15-3.78, P = 0.043) were protective factors for ROSC. Mechanical compression CPR had no significant differences in the rate of ROSC and 24-hour, 7-day, 28-day survival rates for cardiac arrest patients in the emergency departments compared with hands-only compression CPR. For those who undergone CPR duration more than 60 minutes, mechanical compression was associated with a higher rate of ROSC.