Background: Platelet count is a readily available biomarker predicting disease severity and risk of mortality in the intensive care units (ICU). This study aims to describe the frequency, to assess the risk factors, and to evaluate the impact of thrombocytopenia on patient outcomes in a Toxicological ICU (TICU).Methods: In this prospective observational Cohort study, we enrolled 184 patients admitted to our TICU from October 1st, 2019, to August 23rd, 2020. Mild/moderate and severe thrombocytopenia were defined as at least one platelet counts less than 150×103/μL and 50×103/μL during the ICU stay, respectively.Results: Of 184 enrolled patients, 45.7% had mild to moderate thrombocytopenia and 5.4% had severe thrombocytopenia. Old age (OR: 1.042, 95%CI: 1.01-1.075, P=0.01), male gender (OR: 4.348, 95%CI: 1.33-14.22, P=0.015), increased international normalized ratio (INR) levels (OR: 3.72, 95%CI: 1.15-112, P=0.028), and administration of some medications including heparin (OR: 3.553, 95%CI: 1.11-11.36, P=0.033), antihypertensive drugs (OR: 2.841, 95%CI: 1.081-7.471, P=0.034), linezolid (OR: 13.46, 95%CI: 4.75-38.13, P<0.001), erythromycin (OR: 19.58, 95%CI: 3.23-118.86, P=0.001), and colistin (OR: 10.29, 95% CI 1.44-73.69, P=0.02) were the risk factors of hospital-acquired thrombocytopenia. The outcomes of patients with normal platelet count were significantly better than those who developed thrombocytopenia (P<0.001).Conclusion: We found that thrombocytopenia could develop in almost 50% of patients admitted to TICU, which is associated with poor prognosis. Additionally, the platelet counts should be closely monitored to administer some medications (heparin, antihypertensive drug, and linezolid), especially in old patients.