Purpose: Antiplatelet and/or anticoagulant medication use is common. Abstinence a week before surgery may still result in altered hemostasis. The study aim was to report on perioperative antiplatelet and anticoagulant use in thyroidectomy and parathyroidectomy patients, and to determine the association with postoperative hematoma (POH) rates. Methods: Retrospective review of a prospective endocrine surgery database was performed. Procedure extent was defined as unilateral, bilateral, or extensive. Antiplatelets were categorized as none, 325 mg aspirin (ASA), <325 mg ASA, clopidogrel, or other. Anticoagulants were categorized as none, oral, or injectable. Results: A total of 4514 patients were identified. POH developed in 22 patients (0.5 %). Rates were similar between age, gender, and reoperative status. POH were seven times more common after thyroidectomy (0.8 vs. 0.1 %, p < 0.01). Unilateral procedures had lower POH rates than bilateral or extensive (0.1 vs. 0.9 vs. 0.8 %, p < 0.01). POH rates in patients receiving 325 mg ASA (0.8 %) or clopidogrel (2.2 %) were much higher than patients not receiving antiplatelets (0.5 %) or receiving <325 mg ASA (0.1 %, p = 0.04). Oral anticoagulants (2.2 %) and injectable anticoagulants (10.7 %) had much higher POH rates than patients not receiving anticoagulants (0.4 %, p < 0.01). Target organ, patient gender, procedure extent, antiplatelet use, and anticoagulant use were included on logistic regression to determine association with POH. Bilateral procedures, thyroidectomy, clopidogrel, oral, and injectable anticoagulants were all independently associated with POH. Conclusions: POH occur more frequently after thyroidectomy and during bilateral procedures. Patients requiring clopidogrel or any anticoagulant coverage are at much higher risk for POH. These higher-risk patients should be considered for observation to ensure prompt POH recognition and intervention.