AIM: Our study aimed to evaluate the baseline and early follow-up evolution of three inflammatory ratios, namely neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) in patients with Klatskin tumors. MATERIAL AND METHODS: A cohort retrospective study was conducted on consecutive patients with Klatskin tumor who presented in a regional surgical department for seven years (1 January 2012 to 31 December 2018). Raw data regarding the patients’ characteristics and inflammatory biomarkers were collected from the hospital database. The cohort was divided according to the received treatment as surgical resection or palliative treatment (such as surgical drainage, percutaneous biliary drainage, or endoscopic stenting), and the patterns between groups were compared. RESULTS: Fifty-seven patients, age from 39 to 79 years were evaluated. Neutrophil to lymphocyte ratio (NLR) increased significantly after both procedures (P<0.001). Lymphocytes-to-monocytes ratio (LMR) decreased significantly in the follow-up for patients with surgical resection, for Bismuth class III or IV (P=0.0037), and invasion (P<0.001). The baseline NLR (odd ratio OR=1.23, 95% CI: 1.00 to 1.52, P-value = 0.05) and PLR (OR=1.01, 95%CI: 1.00 to 1.01, P-value = 0.06) ratios could be markers for severity of the disease. CONCLUSIONS: Changes in inflammatory ratios as increases in NLR and decreases of LMR (for patients with resection, higher Bismuth class and invasion) were observed in early follow-up in patients with Klatskin tumors. Baseline NLR and PLR values are potential markers in the identification of advanced hilar cholangiocarcinoma but need further investigation.