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 < .001). Long-term complications rates were the same. Conclusions In PTC the addition of routine LNDVI results in lower postablation levels of TG and higher rates of athyroglobulinemia when compared with TT alone. 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. 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. 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.