OBJECTIVE To identify the risk factors affecting the outcome of operations for differentiated and aggressive thyroid carcinoma which may indicate the need for a more aggressive surgical treatment. DESIGN Retrospective study. SETTING University hospital. PATIENTS AND INTERVENTIONS 143 patients underwent total thyroidectomy with or without central neck lymphadenectomy or modified neck dissection. There were 85 papillary, 34 follicular, 6 widely-invasive follicular, 6 insular, five oxyphilic, five tall cell, and two diffuse sclerosing papillary carcinomas. MAIN OUTCOME MEASURE Disease-related survival. RESULTS At 12-years, the survival was 96%, being 98% among patients with differentiated and 83% among those with aggressive carcinoma (p = 0.0006). Insular and oxyphilic carcinomas had the worst prognosis (at 10 years, 67% and 60%, respectively, p < 0.0001). The high-risk age, metastases, and extent score (AMES) group had worse survival than the low-risk group (12 years, 84% compared with 98%, p = 0.001). Among patients with differentiated carcinoma, the low-risk AMES group had also better outcome than those in the high-risk AMES group (at 12 years, 100% compared with 86%, p < 0.0001), but there was no such difference among patients with aggressive disease. Multivariate analysis showed that women (RR 14.28, 95% confidence interval (CI) 1.13 to 180.28), patients with tumours > or = 5 cm in size (RR 9.60, 95%CI 1.01 to 91.43) and AMES high-risk patients (RR 30.17, 95% CI 1.57 to 577.48) had the worst outcome. CONCLUSION In patients with differentiated thyroid carcinoma, total thyroidectomy and, if the AMES score indicates a high risk, central neck lymphadenectomy with or without modified neck dissection, is associated with a favourable outcome. Poorer outcome is expected if the carcinoma is aggressive, and an aggressive surgical approach is advocated as a routine.