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Background: Dysphagia and potential respiratory pathogens in the oral biofilm are risk factors for aspiration pneumonia in nursing home residents. The aim of the study was to examine if the daily application of 0.05% chlorhexidine oral rinse solution is effective in reducing the incidence of aspiration pneumonia in nursing home residents with dysphagia. Associations between background variables (age, gender, dysphagia severity, care dependency, medication use, number of medical diagnoses, teeth and dental implants, and wearing removable dentures) and the incidence of aspiration pneumonia were also examined., Methods: This study is a multicenter study in which for 1 year participants with dysphagia in the intervention group received the usual oral hygiene care with the addition of a 0.05% chlorhexidine oral rinse solution, whereas participants in the control group received only oral hygiene care., Results: Data of 103 participants in 17 nursing homes were analyzed. Survival analysis showed no significant difference in the incidence of pneumonia between both groups (Cox regression, HR = 0.800; 95% CI [0.368-1.737], p = 0.572). Cox regression analysis for Functional Oral Intake Scale (FOIS)-level showed a significant risk of the incidence of pneumonia (HR = 0.804; 95% CI [0.656-0.986], p = 0.036). After adjustment for Group and FOIS-level, Cox multivariate proportional hazard regression analysis showed that the variables age, gender, Care-dependency Scale-score (CDS) number of diseases, medication use, number of teeth, and the presence of dental implants or removable dentures were not significantly associated with the incidence of pneumonia., Conclusions: Chlorhexidine oral rinse solution 0.05% as an adjunctive intervention in daily oral hygiene care was not found to reduce incidence of aspiration pneumonia. The requested number of participants to achieve sufficient power was not established and high drop-out rate and non-structural compliance was present. The power was considered to be sufficient to analyze the associations between the background variables and the incidence of pneumonia in the included nursing home residents with dysphagia. Dysphagia was found to be a risk factor for aspiration pneumonia., Trial Registration: Registration in The Netherlands National Trial Register: TC = 3515. Approval for the study was obtained from the Medical Ethical Committee of the Radboud University Medical Center (NL. nr:41,990.091.12).