Human papillomavirus (HPV) causes cervical cancer and is strongly associated with other anogenital cancers. Multiple-type HPV infection has been associated with lengthier infection and precancerous lesions. Little is known about multiple-type HPV prevalence and associated factors in men. We examined the prevalence of and risk factors for multiple-type HPV in primarily asymptomatic men. Detection of 37 HPV types in male anogenital epithelium and semen was completed in 463 men in two U.S. cities. The proportions of men with multiple HPV of any type and with multiple oncogenic or nononcogenic types were calculated. Factors associated with multiple HPV were evaluated using multinomial logistic regression. Overall, 22.9% of men had multiple-HPV, 8.6% of men had multiple oncogenic types, and 13.4% had multiple nononcogenic types. Greater proportions of samples at the shaft, glans/corona, and scrotum had multiple HPV types (18.7%, 12.8%, and 7.3%, respectively) than did other anogenital sites (all < or =2.8%). Factors independently associated with multiple-type HPV were Hispanic ethnicity [adjusted odds ratio (AOR), 2.45; 95% confidence interval (95% CI), 1.05-5.67], concurrent detection of genital warts (AOR, 10.40; 95% CI, 1.12-96.6), smoking > or =10 cigarettes/d (AOR, 3.00; 95% CI, 1.07-8.43), greater lifetime number of female sexual partners (AOR, 13.73 for > or =21 versus 1-5; 95% CI, 5.34-35.3), and condom use less than half the time (AOR, 2.03; 95% CI, 1.07-3.84). Detection of multiple HPV types in this study of primarily asymptomatic men was common, particularly at external genital sites. Lifetime number of female sex partners, condom use, and smoking were modifiable factors associated with multiple HPV.