AbstractThe Lubricant Investigation in Men to Inhibit Transmission of human papillomavirus (HPV) Infection randomized control trial in gay, bisexual, and other men who have sex with men (gbMSM) found that carrageenan use neither reduced acquisition of anal HPV infections nor influenced infection clearance. To investigate carrageenan's lack of protective effect, we compared the change in anal HPV16 and HPV18 viral loads following carrageenan use against placebo. We restricted our analysis to participants who completed the first four study visits and had a valid baseline sample (n = 161, 54 HIV‐positive). Samples were tested for HPV detection using the linear array PCR assay. HPV16‐ and/or HPV18‐positive samples were tested for viral load using real‐time PCR. For participants who tested HPV16‐ (n = 29) or HPV18‐positive (n = 10) at least once across visits 1−4, we compared the change in type‐specific viral load between study arms using the Mann−Whitney U test. Although the median net change in HPV16 and HPV18 viral loads across visits 1‐4 was higher in the treatment than placebo arm (HPV16: 0.68 vs. 0.18 copies/cell, p = 0.60; HPV18: 18.32 vs. 10.12 copies/cell, p = 0.52), these differences were not statistically significant. Results were similar by HIV status. Carrageenan use did not impact anal HPV16 or HPV18 viral loads, which may further explain its lack of protective effect in gbMSM.