Objective <p>This study investigates the influence of chronic thrombocytopenia on in-hospital outcomes in patients undergoing single-level anterior cervical discectomy and fusion (ACDF) for degenerative cervical myelopathy (DCM).</p> Methods <p>The retrospective analysis included 228,312 patients aged 20 and older undergoing ACDF between 2005 and 2020 from the US Nationwide Inpatient Sample database. Diagnoses and procedures were identified by the International Classification of Diseases codes. Propensity score matching was performed to balance the baseline characteristics of patients with and without chronic thrombocytopenia, and logistic regressions determined the associations between chronic thrombocytopenia and in-hospital outcomes.</p> Results <p>A total of 3515 patients were included. Chronic thrombocytopenia was present in 703 cases. Patients with chronic thrombocytopenia demonstrated significantly higher risks for prolonged length of stay (adjusted odds ratio [aOR] = 2.58, 95% confidence interval [CI]: 2.18–3.07), non-routine discharge (aOR = 3.25, 95% CI: 2.37–4.46), and any major complications (aOR = 7.6, 95% CI: 6.04–9.56). Chronic thrombocytopenia was significantly associated with increased risks of individual complications, including transfusion, acute postoperative hemorrhagic anemia, acute respiratory distress syndrome/respiratory failure, tracheostomy/mechanical ventilation, acute kidney injury, as well as sepsis. These associations are consistently observed among patients younger and older than 60 years and subgroups having comorbidities or not.</p> Conclusions <p>This study provides comprehensive insights into the negative impact of chronic thrombocytopenia on single-level ACDF short-term outcomes. Clinicians should consider thrombocytopenia as a crucial factor influencing postoperative care and should tailor interventions accordingly, regardless of their age or comorbidity burdens.</p>