Background Lymphadenectomy in clinically node-negative papillary thyroid cancer (PTC) is controversial. The aim of this study is to determine whether routine ipsilateral level VI lymphadenectomy (LNDVI) has advantages over total thyroidectomy (TT) alone. Methods A retrospective cohort study was performed. Patients undergoing surgery for clinically node-negative PTC >1 cm were included. Group A had TT and LNDVI. Group B had TT alone. The number of radioiodine treatments and postablative stimulated serum thyroglobulin (TG) levels were compared. Results From 1995 to 2005, 447 patients with clinically node-negative PTC underwent surgery. Group A (n = 56) had TT and LNDVI. Group B (n = 391) had TT alone. Tumor size was equivalent (group A, 20 mm; group B, 23 mm; P = .14) as were MACIS (metastasis, age, completeness of resection, invasion, and size) scores (group A, 4.70; confidence interval, 4.23-5.17; group B, 4.73; confidence interval, 4.4-5.05). Serum postablative TG levels were lower in group A (0.4 μg/L) compared with group B (9.3 μg/L), P = .02. More patients had undetectable TG levels in group A (72%) than in group B (43%) (P 1 cm were included. Group A had TT and LNDVI. Group B had TT alone. The number of radioiodine treatments and postablative stimulated serum thyroglobulin (TG) levels were compared. From 1995 to 2005, 447 patients with clinically node-negative PTC underwent surgery. Group A (n = 56) had TT and LNDVI. Group B (n = 391) had TT alone. Tumor size was equivalent (group A, 20 mm; group B, 23 mm; P = .14) as were MACIS (metastasis, age, completeness of resection, invasion, and size) scores (group A, 4.70; confidence interval, 4.23-5.17; group B, 4.73; confidence interval, 4.4-5.05). Serum postablative TG levels were lower in group A (0.4 μg/L) compared with group B (9.3 μg/L), P = .02. More patients had undetectable TG levels in group A (72%) than in group B (43%) (P < .001). Long-term complications rates were the same. In PTC the addition of routine LNDVI results in lower postablation levels of TG and higher rates of athyroglobulinemia when compared with TT alone.