Objective Chronic subdural hematoma (cSDH) is common, predominantly affects the elderly, often recurs after treatment, and can have serious complications, including death. Inflammation plays an important role in cSDH and it has been previously shown that some laboratory indices are useful as prognostic markers. The aim was to research the role of hematologic and inflammatory markers in cSDH. Materials and Methods A single-center archival database review to retrieve data on cSDH cases operated on between 2018 and 2020, including: (1) sociodemography (age, gender), (2) clinics (Glasgow Coma Score [GCS], anticoagulants, chronic conditions), (3) laboratory (leukocyte, neutrophil, platelet, C-reactive protein, hemoglobin, red cell distribution width [RDW], neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio [PLR], systemic immune-inflammatory index [SII]), (4) cSDH (size, location, midline shift), and (5) treatment (craniotomy/craniostomy, drainage). Primary outcome was Glasgow Outcome Score (GOS) at discharge and at 1 year, and secondary outcomes were 1 year mortality, resurgery, and recurrence. Hematological and inflammatory indices were compared across two cSDH thickness groups. Results Seventy-two patients were included, 25 women and 47 men, median age 77 years. Seventeen (23.6%) patients had chronic anticoagulant treatment. The majority had a chronic comorbidity: 19 (26.4%) diabetes, 48 (66.7%) hypertension, and 56 (77.8%) other chronic diseases. Median preoperative GCS was 15. Median cSDH thickness was 22.9 mm, sidedness was equally distributed, and midline shift occurred in 60 (83.3 %) patients, with median midline shift of 8.4 mm. The majority of patients underwent a single craniostomy (n = 44, 61.1%), and in all patients a subdural drainage was placed. Median GOS at discharge and at 1 year postoperatively was 5. Mortality was 11.1%, and 16.7% of patients were lost to follow-up. Within the 1-year follow-up, 27.8% of patients had disease recurrence, 25% underwent a repeat surgery. In the “above” versus “below” 15 mm cSDH thickness group there were significant differences in P count (211.5 vs. 279.5 × 10⁹/L, p = 0.009), RDW (13.3 vs. 12.6, p = 0.031), SII (1782 vs. 2653, p = 0.025), and PLR (26.2 vs. 36.7, p = 0.042). Conclusion Hematological indices bear a diagnostic and prognostic potential in cSDH management. All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by H.B., S.K., and W.M., H.B., S.K., and K.B., and H.B., J.M.V., A.D., and G.M., respectively. The first draft of the manuscript was written by H.B. and W.M. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The study was approved by the Institutional Review Board. Article published online: 10 September 2024 © 2024. Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India