Background To compare pain, tolerability, and complications associated with fine needle aspiration (FNA) versus core needle biopsy (CNB). Methods FNAs were performed using 23-gauge needles and CNBs were performed using 18-gauge double-action spring-activated needles in 100 patients for each procedure. Patients were asked to record a pain score using a 10-cm visual analog scale and procedure tolerability. Complications and number of biopsies were recorded. Results The median pain scores were similar for the FNA and CNB approaches during and 20 minutes after the biopsy procedures (3.7 vs. 3.6, P=0.454; 0.9 vs. 1.1, P=0.296, respectively). The procedure was tolerable in all 100 FNA patients and in 97 CNB patients (P=0.246). The mean number of biopsies was fewer in the CNB group (1.4 vs. 1.2, P=0.002). By subgroup analysis (staff vs. non-staff), no significant difference was detected in any parameter. There were no major complications in either group, but three patients who underwent CNB had minor complications (P=0.246). Conclusion FNA and CNB show no significant differences for diagnosing thyroid nodules in terms of pain, tolerability, or complications.