Abstract Background Noncardiac chest pain (NCCP) is one of the leading reasons for emergency department visits and significantly limits patients’ daily functioning. The protective effect of physical activity has been established in a number of pain problems, but its role in the course of NCCP is unknown. This study aimed to document the level of physical activity in patients with NCCP and its association with NCCP-related disability in the 6 months following an emergency department visit. Methods In this prospective, longitudinal, cohort study, participants with NCCP were recruited in two emergency departments. They were contacted by telephone for the purpose of conducting a medical and sociodemographic interview, after which a set of questionnaires was sent to them. Participants were contacted again 6 months later for an interview aimed to assess their NCCP-related disability. Results The final sample consisted of 279 participants (57.0% females), whose mean age was 54.6 (standard deviation = 15.3) years. Overall, the proportion of participants who were physically active in their leisure time, based on the Actimètre questionnaire criteria, was 22.0%. Being physically active at the first measurement time point was associated with a 38% reduction in the risk of reporting NCCP-related disability in the following 6 months (ρ = .047). This association remained significant after controlling for confounding variables. Conclusions Being physically active seems to have a protective effect on the occurrence of NCCP-related disability in the 6 months following an emergency department visit with NCCP. These results point to the importance of further exploring the benefits of physical activity in this population.