Cavernous sinus invasion (CSI) by pituitary tumors is associated with subtotal resection and persistent endocrinopathy. The Knosp classification is a magnetic resonance imaging (MRI) tool used to define CSI in the 2017 World Health Organization Classification. However, alternative criteria may have superior diagnostic performance. This study aimed to assess the diagnostic performance of four MRI criteria, using a combination of endoscopy and day 1 MRI as the reference standard for CSI. A cross-sectional study was conducted including patients treated with endoscopic endonasal transsphenoidal surgery for pituitary macroadenomas, recruited from a tertiary pituitary multidisciplinary center in Sydney, Australia between September 2013, and February 2021. The diagnostic performances of four MRI criteria were assessed: the Knosp criteria, percentage encasement of the internal carotid (PEICA), venous compartment obliteration (VCO), and the Fernandez-Miranda classification. Reference CSI was defined using a combination of intraoperative endoscopy and day 1 MRI. A total of 210 cavernous sinuses (105 patients), were analyzed, (51.7 ± 16.3yrs, 43% female), of which 18% had CSI. CSI was best diagnosed by Knosp ≥ 2 (63% sensitivity and 89% specificity), PEICA ≥ 28% (84% sensitivity and 77% specificity) and VCO of ≥ 3 compartments (65% sensitivity and 89% specificity). CSI was unlikely if any of the following signs were present: Knosp < 1, PEICA < 28%, preservation of the medial or superior compartments or sparing of the superior Fernandez-Miranda compartment (negative predictive value 95%, 95%, 94%, 91% and 92% respectively). In conclusion, alternatives to the Knops criteria including PEICA and VCO can aid CSI diagnosis.