Purpose The aim of the study was to provide an updated systematic review of randomized controlled trials that studied the effectiveness of pharmacological and nonpharmacological interventions to prevent aspiration pneumonia in older adults at risk for aspiration. Method The search was conducted in MEDLINE (PubMed), Scopus, and Web of Science databases and the Cochrane Central Register of Controlled Trials, using a protocol registered on PROSPERO (CRD42019139973). Randomized controlled trials of interventions to reduce the incidence of aspiration pneumonia in individuals older than 65 years at risk for aspiration, published between January 2002 and July 2019 and written in English, were included. Two reviewers independently evaluated the methodological quality of studies using the revised Cochrane risk-of-bias tool. Results Thirteen out of 703 articles identified met the eligibility criteria and were included. Six studies focused on pharmacological interventions, three studies focused on dietary interventions and compensatory strategies, one study focused on oral care, two studies focused on multidisciplinary interventions, and one study assessed a screening method. Four studies showed positive and statistically significant effect in reducing aspiration pneumonia but were considered to have unclear or high risk of bias. Three studies showed promising results on the preventive effect of pharmacological interventions. Conclusions The most recent evidence on the prevention of aspiration pneumonia in older adults revealed modest to poor methodological quality. Given the burden of aspiration pneumonia on patients and on the health care systems, the development of larger well-designed trials on this topic is of undoubted importance.