ABSTRACT: The purpose of the study was to compare changes in oral health during intubation until 48 hours after extubation in neuroscience intensive care unit (ICU) patients enrolled in a standard or a comprehensive oral care protocol. The effects of manual toothbrushing (standard group, n = 31) were compared with those of tongue scraping, electric toothbrushing, and moisturizing (comprehensive group, n = 25) in intubated patients in a neuroscience ICU in a 2-year randomized clinical trial. Oral health was evaluated based on the Oral Assessment Guide (OAG) on enrollment, the day of extubation, and 48 hours after extubation. There were no significant differences in the frequency of the oral care protocol. Protocol compliance exceeded 91% in both groups. The total OAG score and all eight categories significantly deteriorated (Friedman test, p < .001, Bonferroni corrected) in the standard oral care group and did not return to baseline after extubation. Large effect sizes were present at all three points in this group. The total OAG score deteriorated during intubation within the comprehensive protocol group (Friedman test, p < .004) but returned to baseline status after extubation. In four categories, the ratings on tongue, mucous membranes, gingiva, and teeth did not deteriorate significantly over time. Published oral care protocols are substandard in promoting and maintaining oral health in intubated patients. A comprehensive oral care protocol, using a tongue scraper, an electrical toothbrush, and pharmacological moisturizers, was more effective for oral hygiene throughout intubation and after extubation than manual toothbrushing alone.