Objective To investigate the relationship between thrombocytopenia after the restoration of spontaneous circulation and short-term prognosis of patients with in-hospital cardiac arrest. Methods The demographic data, post-resuscitation vital signs, post-resuscitation laboratory tests, and the 28-day mortality rate of patients who experienced in-hospital cardiac arrest at the Emergency Department of West China Hospital, Sichuan University between January 1st, 2016 and December 31st, 2016 were retrospectively analyzed. Logistic regression was used to analyze the correlation between thrombocytopenia after the return of spontaneous circulation and the 28-day mortality rate in these cardiac arrest patients. Results Among the 285 patients included, compared with the normal platelet group (n=130), the thrombocytopenia group (n=155) showed statistically significant differences in red blood cell count, hematocrit, white blood cell count, prothrombin time, activated partial thromboplastin time, and international normalized ratio (P<0.05). The 28-day mortality rate was higher in the thrombocytopenia group than that in the normal platelet group (84.5% vs. 71.5%, P=0.008). Multiple logistic regression analysis indicated that thrombocytopenia [odds ratio =2.260, 95% confidence interval (1.153, 4.429), P=0.018] and cardiopulmonary resuscitation duration [odds ratio=1.117, 95% confidence interval (1.060, 1.177), P<0.001] were independent risk factors for 28-day mortality in patients with in-hospital cardiac arrest. Conclusion Thrombocytopenia after restoration of spontaneous circulation is associated with poor short-term prognosis in patients with in-hospital cardiac arrest.