BACKGROUND AND PURPOSE: Clival invasion, a rare but potentially significant complication of pituitary adenoma, is difficult to detect on MR imaging. Because CT is widely used in adjunct guidance of pituitary surgery and it has recently been suggested that preoperative CT may add useful diagnostic information in addition to pituitary MR imaging, we performed the first large cross-sectional imaging study to define the image attributes, clinical correlates, and prognostic implications of clival invasion on CT for pituitary adenoma surgical guidance. MATERIALS AND METHODS: Preoperative CT images from 390 patients with histopathologically diagnosed pituitary macroadenoma were reviewed retrospectively and classified by the presence and degree of clival invasion. Tumor volume, tumor subtype, patient sex, operative complication, and recurrence rates were compared between groups. RESULTS: After we corrected for multiple correlations, the most significant independent risk factor for clival invasion was female sex (OR = 3.62, P = .014, multinomial logistic regression), followed by large tumor volume (OR = 1.08, P < .001), and null-cell subtype (OR = 5.47, P < .001). Larger tumor volume correlated with null-cell subtype (Mann-Whitney U test, P = .006), incidence of clival invasion (P < .001), and extent of clival invasion (P = .038). Clival invasion was associated with a significantly higher ratio of operative complications (15.63%, chi(2) = 7.067, P = .008) and recurrence (57.14%, chi(2) = 10.739, P = .001). CONCLUSIONS: CT detection of clival invasion by pituitary macroadenoma is significantly more common in women, in patients with large tumors, and in patients with null-cell tumors, and it is associated with a higher rate of operative complications and recurrences. Attention to the presence of clival invasion on preoperative CT and prospective investigation of its prognostic significance are indicated. Attention to this finding on pituitary guidance CT is warranted.