Background <p>Endoscopic transsphenoidal surgery is indicated when non-functioning pituitary adenomas (NFPAs) cause visual compromise, but its timing is less certain in patients with preserved vision and intact pituitary function, where the risk of new post-operative pituitary dysfunction influences decision-making. This systematic review aimed to determine the rate of new post-operative endocrine deficits following transsphenoidal surgery for NFPAs and to identify predictive factors.</p> Methods <p>This review followed PRISMA guidelines. Studies reporting predictors of post-operative endocrine deterioration in adults undergoing transsphenoidal surgery for NFPAs were included. Predictors were synthesised narratively, with meta-analysis where at least two studies used comparable definitions. Pooled proportions estimated the overall rate of deterioration. Certainty of evidence was assessed using GRADE.</p> Results <p>Eleven studies comprising 2,350 patients were included. The pooled proportion developing new post-operative endocrine deterioration was 16% (95% CI 13–20%; I² = 60%). Larger tumour volume was associated with deterioration, and gross total resection with reduced odds compared with subtotal resection. Cavernous sinus invasion and other predictors showed inconsistent associations, while age, sex, comorbidities, apoplexy, pituitary gland or stalk visibility, surgeon experience and surgical approach were not associated with risk. Overall certainty of evidence was low to very low.</p> Conclusion <p>New post-operative endocrine deficits affect approximately one in six patients after transsphenoidal surgery for NFPAs. Tumour volume was the most consistent predictor of endocrine deterioration, suggesting a potential role for earlier intervention in selected patients, although evidence certainty was low to very low. Standardised reporting and prospective studies are needed to guide risk stratification decision-making.</p>