Purpose Headache is common among patients with pituitary adenomas undergone endoscopic endonasal surgery (EES), but was seldomly concerned before. The present study aims to investigate the incidence and profile of risk factors of headache after EES.Methods A meta-analysis was performed to evaluate the occurrence proportions of postoperative headache in patients with pituitary adenomas. Then, a cohort of 101 patients undergone EES were enrolled for analyzing risk factors of headache. The Headache Impact Test (HIT-6) was used to score the headache preoperatively, 1 month and 3 months postoperatively. Results A total of 18 studies and 4442 participants were included for meta-analysis. The pooled occurrence proportion of postoperative headache was 29% (95% confidential interval: 20-38%). For the 101 patients enrolled in the present study, 26 (25.74%) of them had a HIT-6 scores of > 55 preoperatively, but decreased to 22 (21.78%) at 1 month, and 6 (5.94%) at 3 months, postoperatively. Multivariate analysis showed that pituitary apoplexy (OR=3.591, 95%CI 1.219-10.575, p=0.020) and Hardy's grade C-D (OR=21.06, 95%CI 2.25-197.02, p=0.008) were independently risk factors for preoperative headache. In contrast, postoperative sinusitis (OR=3.88, 95%CI 1.16-13.03, P=0.028) and Hardy's grade C-D (OR=10.53, 95%CI 1.02-109.19, P=0.049) independently predicted the presence of postoperative headache at 1 month. At 3 months postoperatively, the proportion of sinusitis tended to be higher in the headache group than the one in non-headache group (100% vs. 30.0%, p=0.070). Conclusion Headache is very common following EES for pituitary adenomas. Prophylactic management of postoperative sinusitis may help to alleviate postoperative headache.