Background <p>Enlarged perivascular spaces (EPVS) are recognized as important imaging markers of impaired cerebral waste removal. However, the relationship between cerebral venous outflow disorder (CVOD) and EPVS has not yet been established.</p> Methods <p>A total of 191 patients were enrolled, comprising 35 non-CVOD cases and 156 CVOD cases. The CVOD group was further stratified into three subgroups based on venous sinus characteristics and stenosis location: asymmetrical sinus with inferior stenosis (AS-IS), symmetrical sinus with unilateral/bilateral stenosis (SS-US/BS), and asymmetrical sinus with dominant stenosis (AS-DS). EPVS in the basal ganglia (BG) and centrum semiovale (CSO) were visually rated using a semi-quantitative scale and subsequently categorized into low-degree (scores 0–1) and high-degree (scores 2–4). Univariate and multivariate Firth logistic regression analyses were performed to evaluate the association of CVOD subtypes with EPVS severity.</p> Results <p>Multivariate Firth logistic regression identified that age (adjusted OR 1.080, 95% CI 1.037–1.131, p &lt; 0.001), mild stenosis of intracranial arteries (ICA) or extracranial arteries (ECA) (adjusted OR 3.725, 95% CI 1.076–12.601, p = 0.038), and AS-DS (adjusted OR 5.152, 95% CI 1.257–31.747, p = 0.021) were independently associated with high-degree BG-EPVS. Meanwhile, AS-DS was the sole independent predictor of high-degree CSO-EPVS (adjusted OR 3.971, 95% CI 1.567–10.885, p = 0.003).</p> Conclusions <p>Positive associations were observed between AS-DS and high-degree BG-EPVS and CSO-EPVS, underscoring the potential involvement of the cerebral venous outflow system in perivascular waste clearance.</p> <p><i>Trial registration</i> This study has been registered with the Chinese Clinical Trial Registry (ChiCTR) under the registration number ChiCTR2500106960, with a registration date of August 1, 2025</p>