We aimed to evaluate the clinical characteristics and outcome, hospital stay, and intracranial hemorrhage (ICH) development of patients with cerebral venous sinus thrombosis (CVST) who presented with isolated headache. In a retrospective study, consecutive patients with a definite diagnosis of CVST referred to Namazi hospital (Shiraz University of Medical Sciences) from 2012 to 2016 were included. Clinical, radiological, and prognostic characteristics and outcome on discharge (using modified Rankin Scale (mRS)) were compared between the CVST patients who presented with isolated headache and other CVST patients through univariate analyses. The associations of isolated headache with poor outcome (mRS > 2), presence or development of ICH, and duration of hospital stay were assessed through multivariable analyses. Of the 174 patients, 45 (26.0%) presented with isolated headache. Presence of isolated headache was more frequent in men ( p value = 0.048) and patients with thrombophilia ( p value = 0.040). Lateral sinus involvement was more common in patients with isolated headache ( p value = 0.005). After adjustment for other variables, the isolated headache was significantly associated with shorter hospital stay (odds ratio (OR): 0.85, confidence interval (CI): 0.73–0.99) and lower risk of early ICH (OR: 0.314, CI: 0.132–0.749). Although poor outcome was significantly less frequent in patients with isolated headache on univariate analysis ( p value < 0.001), this association was not significant in multivariable analysis (OR: 0.324, CI: 0.035–2.985). CVST patients with isolated headache had lower ICH events and shorter hospital stay. CVST should be considered as a possible differential diagnosis in certain patients who present only with headache, particularly those with diffuse progressive headache, or underlying provocative conditions.