Objective: To analyze the clinical features and risk factors of tigecycline-associated thrombocytopenia. Methods: A retrospective case-control study of patients who were treated with tigecycline was conducted between January 2018 and June 2022. Results: A total of unique 506 patients were screened in this study. 12.3% of patients experienced thrombocytopenia. thrombocytopenia developed 2 to 22 days after the initiation of tigecycline, with a median (25-75th percentile) of 9 (6–11) days. Mild to moderate (grades 1-2) thrombocytopenia occurred in 60.9% (28/46) patients and severe (grades 3-4) thrombocytopenia occurred in 39.1% (18/46) patients. In the multivariate analysis, age≥74 years (p=0.028), risk of malnutrition (p<0.001), tigecycline therapy for ≥7 days (p=0.003), DBIL>8.1μmol/L (p<0.001)), BUN>8.1mmol/L (p=0.002) were independent risk factors associated with thrombocytopenia. 70.7% (65/92) of patients in the control group had 0-2 risk factors. Whereas in the thrombocytopenia group, all patients had risk factors and 95.7% (44/46) had 3 to 5 risk factors, only 4.4%(2/46) of patients had 0-2 risk factor. Conclusion: Tigecycline administration was associated with thrombocytopenia. Health professionals should be aware of the potentially severe tigecycline-associated thrombocytopenia and monitor platelet count level, especially when the patients have more than 3 risk factors.