Objective There is no pharmacological treatment for oropharyngeal dysphagia (OD). The aim of this study was to compare the therapeutic effect of stimulation of oropharyngeal transient receptor potential vanilloid type 1 (TRPV1) with that of thickeners in older patients with OD. Design A clinical videofluoroscopic non-randomised study was performed to assess the signs of safety and efficacy of swallow and the swallow response in (1) 33 patients with OD (75.94±1.88 years) while swallowing 5, 10 and 20 ml of liquid (20.4 mPa.s), nectar (274.4 mPa.s), and pudding (3930 mPa.s) boluses; (2) 33 patients with OD (73.94±2.23 years) while swallowing 5, 10 and 20 ml nectar boluses, and two series of nectar boluses with 150 μM capsaicinoids and (3) 8 older controls (76.88±1.51 years) while swallowing 5, 10 and 20 ml nectar boluses. Results Increasing bolus viscosity reduced the prevalence of laryngeal penetrations by 72.03% (p<0.05), increased pharyngeal residue by 41.37% (p<0.05), delayed the upper esophageal sphincter opening time and the larynx movement and did not affect the laryngeal vestibule closure time and maximal hyoid displacement. Treatment with capsaicinoids reduced both, penetrations by 50.% (p<0.05) and pharyngeal residue by 50.% (p<0.05), and shortened the time of laryngeal vestibule closure (p<0.001), upper esophageal sphincter opening (p<0.05) and maximal hyoid and laryngeal displacement. Conclusion Stimulation of TRPV1 by capsaicinoids strongly improved safety and efficacy of swallow and shortened the swallow response in older patients with OD. Stimulation of TRPV1 might become a pharmacologic strategy to treat OD.