This study, conducted as part of the National Health and Nutrition Examination Survey (NHANES) 2009–2010, aimed to determine the prevalence of oral human papillomavirus (HPV) infection in the United States. The study included 5579 participants aged 14 to 69 years, who provided oral rinse samples for HPV detection. The overall prevalence of oral HPV infection was 6.9%, with a higher prevalence among men (10.1%) compared to women (3.6%). HPV-16 was detected in 1.0% of participants. The prevalence of oral HPV infection followed a bimodal age pattern, with peaks at ages 30 to 34 and 60 to 64 years. Factors associated with oral HPV infection included age, sex, number of sexual partners, and smoking intensity. The study highlights the importance of sexual behavior and smoking as modifiable risk factors for oral HPV infection and suggests that targeted prevention strategies may be feasible.This study, conducted as part of the National Health and Nutrition Examination Survey (NHANES) 2009–2010, aimed to determine the prevalence of oral human papillomavirus (HPV) infection in the United States. The study included 5579 participants aged 14 to 69 years, who provided oral rinse samples for HPV detection. The overall prevalence of oral HPV infection was 6.9%, with a higher prevalence among men (10.1%) compared to women (3.6%). HPV-16 was detected in 1.0% of participants. The prevalence of oral HPV infection followed a bimodal age pattern, with peaks at ages 30 to 34 and 60 to 64 years. Factors associated with oral HPV infection included age, sex, number of sexual partners, and smoking intensity. The study highlights the importance of sexual behavior and smoking as modifiable risk factors for oral HPV infection and suggests that targeted prevention strategies may be feasible.