Prognostic factors in patients with primary chronic subdural hematoma (CSDH) taking the natural course are unclear. To identify independent influencing factors of wait-and-watch management, a case–control study of moderate CSDH patients using wait-and-watch as monotherapy in a single center from February 2014 to November 2021 was conducted. A total of 39 patients who responded to wait-and-watch management (cases) and 24 nonresponders (controls) matched for age, sex, height, weight, MGS-GCS (Markwalder grading scale and Glasgow Coma Scale), and bilateral hematoma were included. Demographics, blood cell counts, serum biochemical levels, imaging data, and relevant clinical features at baseline were collected. Significant differences between cases and controls were found in the hematoma volume, ability to urinate, maximal thickness of the hematoma, and hypodensity of the hematoma in univariate analysis. Hypodense hematoma and hematoma volume were independently associated with the outcome in multivariate analysis. Combining these independently influencing factors revealed an area under the receiver operator characteristic curve of 0.741 (95% CI: 0.609-0.874, sensitivity = 0.783, specificity = 0.667). These findings may contribute to the early detection of patients with moderate CSDH who may respond to wait-and-watch strategies. Although wait-and-watch tactics could work sometimes, medical interventions, including drug treatment, should be recommended in the clinic.