Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor, with an increasing incidence worldwide, particularly in Asia. Although radical surgical resection is currently the only potentially curative treatment, the high recurrence rate and low postoperative overall survival (OS) rate of ICC remain major clinical challenges. Adjuvant therapy (AT) and neoadjuvant therapy (NAT) are important strategies to reduce postoperative recurrence and prolong OS. Several studies have shown certain efficacy of these treatments. However, the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation. This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis, so as to provide scientific evidence for optimizing treatment strategies.Methods The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected. Patients were grouped based on their treatment modality: NAT+AT group, AT group, and non-NAT/AT group. The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching (PSM) to balance baseline data. The Kaplan-Meier method was used to analyze OS and disease-free survival (DFS), and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results A total of 395 ICC patients were included in the final analysis, with 42 patients (10.6%) in the NAT+AT group, 62 patients (15.7%) in the AT group, and 291 patients (73.7%) in the non-NAT/AT group. Before PSM, significant differences were observed between groups in terms of CA19-9, liver function Child-Pugh classification, intraoperative blood loss, surgical margin, differentiation grade, vascular invasion, ECOG score, and lymph node dissection ratio (all P<0.05). After PSM, there were no significant differences in baseline characteristics between the groups (all P>0.05). After matching, the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups (both P<0.05), while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups (both P>0.05). Subgroup analysis showed that in TNM stage I patients, DFS in the NAT+AT group was significantly better than in the non-NAT/AT group (P<0.05), but OS was not significantly different (P>0.05). In TNM stage Ⅱ and Ⅲ patients, both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group (both P<0.05), and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients (P<0.05).Conclusion NAT combined with AT provides better survival benefits for patients with locally advanced ICC, but its benefit for early-stage ICC patients is limited. However, the retrospective design and sample size limitations of this study may affect the stability of the results, and future large-sample, multicenter, prospective studies are needed for further validation.