Background Tooth loss has been linked to poor health such as chronic diseases and mobility limitations. Prospective evidence on the association between tooth loss and walking speed decline is however lacking.AimsTo examine the impact of tooth loss on walking speed over time and explore whether inflammation may account for this association.MethodsThis study included 2695 persons aged 60 years and older, who were free from severe mobility limitation at baseline. Information on dental status was assessed through self-report during the nurse interview at baseline. Walking speed baseline and at 3- and 6-year follow-ups was assessed when participants walked at their usual pace. Covariates included age, sex, education, lifestyle-related factors, and chronic diseases. Blood samples were taken, and C-reactive protein (CRP) was tested.ResultsAt baseline, 389 (13.1 %) participants had partial tooth loss and 204 (6.9 %) had complete tooth loss. Mixed-effects models showed that tooth loss was associated with a greater decline in walking speed over time after adjustment for lifestyle-related factors and chronic diseases (p = 0.001 for interaction between time and tooth loss on walking speed decline); however, when further adjusting for inflammation (CRP), the association was attenuated and no longer significant.ConclusionTooth loss was associated with an accelerated decline in walking speed in older adults. Inflammation may play a role in the association between tooth loss and walking speed decline.