Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors. However, the safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remain unclear. Thus, we conducted an updated meta-analysis to evaluate the efficacy and safety of LPD versus OPD in patients with periampullary tumors, with a particular focus on the pancreatic ductal adenocarcinoma patient subgroup. According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Endpoints and sensitive analysis were conducted for short-term endpoints. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. Five RCTs yielding 1018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to the LPD group. Total follow-up time was 90days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2 = 87%; Fig.1A), lower intraoperative blood loss (MD - 124.05; 95% CI - 178.56 to - 69.53; p < 0.001; I2 = 86%; Fig.1B), and shorter length of stay (MD - 1.37; 95% IC - 2.31 to - 0.43; p = 0.004; I2 = 14%; Fig.1C) as compared with OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.