Background and Aims The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in recent years. Due to its insidious onset and low rate of early diagnosis, radical resection remains the only potential curative treatment. Lymph node metastasis is a major adverse prognostic factor in ICC, but the scope and therapeutic value of lymphadenectomy remain controversial. Previous studies suggest that patients with central ICC may derive greater survival benefit from lymphadenectomy than those with peripheral ICC. Preoperative assessment of lymph node status mainly relies on imaging, but its accuracy is limited. This study aimed to investigate the prognostic impact of lymphadenectomy in ICC patients at different anatomical sites to inform surgical decision-making.Methods A retrospective analysis was conducted on 220 ICC patients who underwent radical resection at the 904th Hospital of the Joint Logistic Support Force of the PLA from May 2016 to May 2021. The cohort included 126 males and 94 females, with a mean age of (56.76±13.15) years. Patients were categorized into peripheral ICC (n=144) and central ICC (n=76) groups. Clinical characteristics, albumin-bilirubin (ALBI) grade, preoperative risk of lymph node metastasis, number of lymph nodes dissected, lymph node metastasis status, and postoperative survival outcomes were compared. Subgroup analyses were conducted to assess the prognostic value of the number of lymph nodes dissected under different risk stratifications.Results Significant differences were observed between peripheral and central ICC in ALBI grade (χ²=9.952, P=0.002), preoperative lymph node metastasis risk (χ²=6.166, P=0.014), number of lymph nodes dissected (χ²=4.167, P=0.042), and lymph node metastasis rate (χ²=7.331, P=0.007). The 3-year overall survival (OS) rate was higher in peripheral ICC (31.94%) than in central ICC (15.79%) (χ²=13.890, P<0.001). Among central ICC patients, those with ≥6 lymph nodes dissected had better 3-year OS than those with <6 (16.89% vs. 13.04%, χ²=3.894, P=0.048). In the high-risk subgroup of central ICC, ≥6 lymph nodes dissected was also associated with improved 3-year OS compared with <6 (15.62% vs. 11.11%, χ²=3.962, P=0.047). In contrast, the number of lymph node dissections had no significant prognostic impact in peripheral ICC or in patients classified as low risk.Conclusion Patients with peripheral ICC had a better prognosis than those with central ICC. Adequate lymphadenectomy (≥6 nodes) improved survival and enhanced staging accuracy in central ICC patients at high risk of lymph node metastasis, highlighting the importance of preoperative risk assessment for optimizing surgical strategies.