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Background Current studies did not draw definitive conclusions on comparison of intracorporeal anastomosis (ICA) with extracorporeal anastomosis (ECA) in laparoscopic right colectomy. Whether the intraperitoneal contamination induced by ICA can result in higher risk of postoperative abdominal infection remains unclear. This study was aimed to compare the short‐term outcomes, especially the risk of abdominal infection after ICA versus ECA. Methods This was an observational cohort study as a secondary analysis of a randomized controlled trial (RCT)—RELARC trial (NCT02619942). The patients enrolled in the RELARC trial were diagnosed with primary colon adenocarcinoma without distant metastasis and underwent radical laparoscopic right colectomy between Jan 2016 and Dec 2019. In our study the patients who converted to open surgery in RELARC trial were excluded. The short‐term outcomes were compared between ICA and ECA. The primary endpoint was abdominal infection. The inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) was used for adjusting the potential confounders. Results This study enrolled 975 patients with 119 patients undergoing ICA and 856 patients undergoing ECA. The incidence of abdominal infection was higher in ICA group (9.2% versus 1.5%, RR from IPTW = 5.7 (95%CI: 2.6–12.6), P < 0.001) as well as the incidence of wound infection (14.3% vs 3.3%, RR from IPTW = 5.0 (95%CI: 2.9–8.6), P < 0.001). ICA was associated with higher incidence of Clavien–Dindo (CD) grade I and II complications (CD‐I: 15.1% versus 6.8%, RR from IPTW = 2.4 (95%CI: 1.5–3.9), P < 0.001; CD‐II: 26.9% versus 8.2%, RR from IPTW = 3.6 (95%CI: 2.5–5.1), P < 0.001) but similar incidence of CD‐III ~ IV complications compared to ECA (3.4% vs 2.1%, RR from IPTW = 1.2 (95%CI: 0.4–4.0), P = 0.73). In ICA group, choosing another incision rather than lengthening main port site decreased the incidence of wound infection although without statistical significance (17.3% (14/81) versus 7.9% (3/38), crude RR = 2.2 (95%CI: 0.7–7.2), P = 0.17). Conclusion ICA is likely to be associated with higher risk of abdominal infection and CD‐I ~ II complications.

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