Background and Aims The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in recent years. This disease often presents insidiously with few obvious symptoms, leading to a low rate of early diagnosis. Radical resection remains the only potential curative treatment, but due to reasons such as widespread tumor metastasis, inadequate residual liver reserve, and poor general condition of patients, the rate of radical resection is low. Therefore, this study was performed to investigate the relationship between the number of positive lymph nodes and the postoperative prognosis of ICC patients, in order to provide references for the prognosis evaluation of ICC surgery and guidance for postoperative treatment strategies.Methods The clinical data of 150 ICC patients undergoing radical resection in the Department of Hepatobiliary Surgery, the 904th Hospital of Joint Logistic Support Force of PLA from September 2017 to September 2020 were retrospectively collected. Factors influencing postoperative survival of patients and the differences in postoperative survival among patients with different numbers of positive lymph nodes (N0: no lymph node metastasis; N1: less than 3 lymph node metastases; N2: 3 or more lymph node metastases) were analyzed.Results Univariate analysis showed that preoperative levels of CA19-9 and AFP, margin status, and the number of positive lymph nodes were significantly associated with postoperative survival of ICC patients (all P<0.05). Multivariate analysis revealed that margin status (P=0.003), preoperative CA19-9 level (P=0.008), and the number of positive lymph nodes (P<0.001) were independent risk factors affecting postoperative prognosis. The 1-, 2-, and 3-year postoperative survival rates of all 150 ICC patients were 50.67%, 24.67%, and 17.33%, respectively. The survival rates of 62 N0 patients were 79.03%, 43.55%, and 32.25% at 1, 2, and 3 years, respectively; those of 36 N1 patients were 47.22%, 27.78%, and 16.67%, respectively; and those of 52 N2 patients were 19.23%, 0, and 0, respectively. There was a statistically significant difference in overall survival among the three groups with different lymph node profiles (χ²=33.516, P<0.001), and the survival rates sequentially decreased in N0, N1, and N2 patients (all P<0.05).Conclusion The number of positive lymph nodes is an independent risk factor influencing the postoperative prognosis of ICC patients. Using 3 positive lymph nodes as a cutoff value, combined with assessment of other relevant factors, can improve the risk stratification of ICC patients in clinical practice and provide a theoretical basis for postoperative treatment strategies for ICC.