This prospective randomised double-blind multicentre study evaluated whether postoperative antibiotics resulted in improvement in sinonasal quality of life (QoL) compared to placebo in patients undergoing endoscopic endonasal transsphenoidal pituitary surgery. A total of 461 patients were screened for the study and 131 were randomised. Sinonasal QoL at two weeks was measured primarily on the Anterior Skull Base Nasal Inventory-12. Secondary measures included sinonasal QoL reported on the Sinonasal Outcome Test-22 and objective endoscopy scores with Lund-Kennedy method to assess nasal healing. The study did not find any statistical difference in sinonasal QoL after postoperative prophylactic antibiotics compared to placebo amongst the two groups of patients. Nasal cavity endoscopy scores were also not different between the two groups at one-to-two weeks or at three-to-four weeks after surgery. Nasal toilet, and in-office clearing of the sinonasal passages are likely to contribute rather than the antibiotics.