OBJECTIVE: We examined the influence of liquid thickness levels on the frequency of liquid penetration-aspiration in patients with dysphagia and evaluated the clinical risk factors for penetration-aspiration and aspiration pneumonia development. STUDY DESIGN: A case series. SETTING: Single-institution academic center. METHODS: We reviewed medical charts from 2018 to 2019. First, we evaluated whether liquid thickness levels influence the frequency of liquid penetration-aspiration in patients with dysphagia. Penetration-aspiration occurrence in a videofluoroscopic swallowing study was defined as Penetration-Aspiration Scale (PAS) scores ≥3. Second, the association between liquid thickness level and penetration-aspiration was analyzed, and clinical risk factors were identified. Moreover, clinical risk factors for aspiration pneumonia development within 6 months were investigated. RESULTS: Of 483 patients, 159 showed penetration-aspiration. The thickening of liquids significantly decreased the incidence of penetration-aspiration (P < .001). Clinical risk factors for penetration-aspiration were vocal fold paralysis (odds ratio [OR], 1.99), impaired laryngeal sensation (OR, 5.01), and a history of pneumonia (OR, 2.90). Twenty-three patients developed aspiration pneumonia while undertaking advised dietary changes, including liquid thickening. Significant risk factors for aspiration pneumonia development were poor performance status (OR, 1.85), PAS score ≥3 (OR, 4.03), and a history of aspiration pneumonia (OR, 7.00). CONCLUSION: Thickening of liquids can reduce the incidence of penetration-aspiration. Vocal fold paralysis, impaired laryngeal sensation, and history of aspiration pneumonia are significant risk factors of penetration-aspiration. Poor performance status, PAS score ≥3, and history of aspiration pneumonia are significantly associated with aspiration pneumonia development following recommendations on thickening liquids. LEVEL OF EVIDENCE: 3.