Background Although randomized studies investigated the benefit of extended lymphadenectomy (ELA) compared to standard lymphadenectomy (SLA) for periampullary adenocarcinoma, these analyses failed to show overall advantage for ELA due to high heterogeneity of lymphadenectomy protocols. Therefore, the present single-center trial was designed using a standardized protocol for SLA with en bloc technique.Methods Patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma were randomized to either SLA or ELA. Primary study endpoint was recurrence-free survival. Secondary endpoints were overall survival as well as peri-and postoperative morbidity and mortality.Results Sixty-six out of 103 randomized patients were treated by SLA (n = 34) or ELA (n = 32) and included into final data analysis. ELA compared to SLA resulted in a higher number of removed lymph nodes (25 ± 12 vs. 14 ± 8; p < 0.001) with a comparable number of lymph node metastases (3 ± 5 vs. 2 ± 3). Median recurrence-free survival was comparable between SLA (18.7 months) and ELA (11.3 months) p = 0.445. Median overall survival was 22.1 months in the SLA group and 15.5 months in the ELA group. Overall survival rates after 9 and 18 months for SLA were 76.5 and 55.6 % and for ELA 68.8 and 46.9 %, respectively.Conclusion ELA for periampullary carcinomas resulted in a higher number of resected lymph nodes. This radical approach showed no benefit in terms of median recurrence-free and overall survival and therefore cannot be recommended in general.