BACKGROUND: The impact of preoperative neck ultrasound (US) on management of the lateral neck in patients with differentiated thyroid cancer is unclear. The objective of this study was to assess the impact of preoperative neck US on the rate of lateral neck dissection in clinical N0 neck and initial response to therapy. METHODS: An institutional review board-approved retrospective review of 890 patients that had thyroid surgery for differentiated thyroid cancer between 2009 and 2010 was performed at our institution. Patients with palpable neck disease, distant metastases, less than total thyroidectomy, no postoperative thyroglobulin (Tg) determinations, and positive Tg antibodies were excluded, leaving 465 patients available for analysis. Patients were divided into those who had a preoperative neck US to evaluate lateral neck nodes (n = 234) and those who did not (n = 231). Patient and tumor characteristics were compared using the χ(2) test. The primary end point was response to therapy, defined by postoperative US and Tg levels. RESULTS: There were no significant differences in age, histology, T stage, postoperative radioactive iodine dose, American Joint Committee on Cancer stage, American Thyroid Association risk category, or duration of follow up between the 2 groups. Patients with preoperative neck US were more likely to have lateral neck dissection compared with patients without preoperative neck US [n = 31 (13.2%) vs n = 2 (0.9%); P < .001]. Preoperative neck US resulted in a better response to therapy (P = 0.005), a greater likelihood of no evidence of disease, and a smaller likelihood of having a biochemical or structural incomplete response or a return for delayed neck dissection. The preoperative US group also resulted in fewer recurrences; 10 patients from the no preoperative US group returned to the operating room compared with two patients (4.3% vs 0.9%, P = .018) who had a preoperative neck US. CONCLUSION: Preoperative neck US detects more lateral neck disease, leading to an increase in lateral neck dissection with subsequent improvement in response to therapy and fewer return to the operating room for regional recurrence management.