Headache is a common symptom among patients with pituitary tumors, as it is in the general population. The aim of the study was to investigate headache as a symptom in patients with pituitary tumors before and 6 months after endoscopic transsphenoidal surgery (TSS).  This is a prospective observational cohort study.  This study was conducted at university tertiary referral hospital.  A total of 110 adult patients underwent endoscopic TSS for pituitary tumors.  The Migraine Disability Assessment (MIDAS) questionnaire was used before and 6 months after surgery for the assessment of headache. Clinical variables with potential influence on headache were analyzed.  Sixty-eight (62%) patients experienced headaches at least once during the 3 months before surgery. Thirty (27%) patients reported disabling headache before surgery, with younger age being an independent associated factor (  < 0.001). In patients with disabling headache before surgery, the median (interquartile range) MIDAS score improved from 78 (27-168) to 16 (2-145;  = 0.049), headache frequency decreased from 45 (20-81) to 14 (4-35) days (  = 0.009), and headache intensity decreased from 6 (5-8) to 5 (4-7) (  = 0.011) after surgery. In total, 16 of the 30 (53%) patients reported a clinically relevant improvement and five (17%) a clinically relevant worsening. Four (5%) patients developed new disabling headache. No predictor for postoperative improvement of headache was identified.  In this prospective study, the results show that disabling headache improves following endoscopic TSS in a subset of patients with pituitary tumors. However, no predictive factors for improvement could be identified.