Objectives To assess the effect of major salivary gland intraductal irrigations (IGs) to relieve mouth dryness. Methods We retrospectively analyzed the records of patients with mouth dryness who underwent major salivary gland IG during 2013–2015. Records included demographics, medical background, dry mouth etiologies and symptomatology, and results of sialometry and sialo‐cone‐beam computerized tomography. Subjective improvement following the IG procedure (yes/no) and sustained subjective improvement (mouth dryness relief for ≥1 month) were recorded. Objective improvement was assessed by comparing the mean unstimulated (USF) and stimulated (SSF) whole salivary flow (WSF) rate before and after the IG. Results Seventy‐four patients were included [mean age: 59.08 ± 12.46 years]. Improvement was detected in the USF (p = .027), but not in the SSF (p = .878). Fifty‐five (84.6%) noted subjective improvement, while 10 (15.4%) did not. Subjective improvement was positively associated with the USF following IG (p = .037), with salivary gland swelling episodes (p = .033), and with difficulties in swallowing dry foods (p = .014). Of those with subjective improvement, 45 (81.8%) reported sustained improvement, which was positively associated with lack of a gritty eye sensation (p = .042) and abnormal sialo‐CBCT findings (p = .001). Conclusions Major salivary gland IG is a simple and safe procedure that may relieve dry mouth for a relatively extended duration. Further studies are needed to confirm these preliminary findings and assess their underlying mechanisms.