Anti-inflammatory treatment reduces the risk of recurrent chronic subdural hematoma (CSDH), but clinical implementation is improper due to side effects. Exact knowledge of subdural molecules involved in recurrent CSDH may lead to targeted medical treatment and possibly improve the prospect of a personalized approach by eliminating the broad use of anti-inflammatory drugs on the entire CSDH population. With this study, we aim to (1) describe the associations between cytokine levels at the primary surgery and the risk of subsequent recurrence and (2) describe the association between cytokines in patients with recurrent CSDH between the first and second operations. Systemic and subdural levels of pro- and anti-inflammatory cytokines were measured and compared between patients with the first-time CSDH and recurrent CSDH. Cytokine levels were analyzed using a multiplex antibody bead kit. In case of recurrent CSDH within 90 days of follow-up, the samples were re-collected and analyzed. We included 101 adult CSDH patients of which 20 had a recurrence. The levels of cytokines in the CSDH fluid from patients who were operated on for the first-time CSDH were not associated with the risk of later developing a recurrence. We found interleukin-1 receptor antagonist (IL-1ra) to be elevated in subdural fluid in patients with recurrent CSDH at the time of their second operation (p = 0.0005). This study provides knowledge on cytokine composition in the subdural fluid in patients with CSDH with and without recurrence. IL-1ra is elevated in subdural fluid in patients with recurrent CSDH at the time of the second operation, identifying a possible medical target.