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Objectives Tattooing is not an evolved behavior, but it may be a phenotypic gambit to highlight immunological health. Phenotypic gambits are traits or behaviors that appear costly but occur at high rates as a honing process of natural selection not constrained by genetics. Tattooing is an ancient practice that is increasing in popularity worldwide, but it involves wounding the body, which seems counterintuitive because it challenges the immune system and makes one more susceptible to infection. But tattooing may represent a costly honest signal of fitness by “upping the ante” in an era of hygiene or a means to stimulate the immune system in a way that improves and highlights underlying fitness. Materials and Methods We investigated this hypothesis by assessing bacteria killing activity (BKA) in saliva samples collected during two studies of tattooing (N = 40). We compared previous tattoo experience (extent of body tattooed and hours spent being tattooed) to BKA before and after getting a new tattoo. Results Tattoo experience positively predicts post-tattoo BKA (β = 0.48, p = 0.01), suggesting that people with more tattoo experience have a relatively more immediate and active immune response than those with less tattoo experience. Discussion Tattoo experience may elevate innate immunological vigilance, which could aid in protecting against future dermal insults.