Respiratory syncytial virus associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in adults, especially in those with comorbidities. We aimed to identify all studies worldwide investigating the disease burden of RSV-ARI in adults with comorbidities. We estimated the community incidence, hospitalisation rate and in-hospital case fatality ratio (hCFR) of RSV-ARI in adults with comorbidities based on a systematic review of studies published between January 1996 and March 2020. We also investigated the strength of the association between RSV-ARI and any comorbidity in adults. Meta-analyses based on random effects model were carried out to generate the estimates. The disease burden of RSV-ARI among adults with comorbidity is substantial with limited data available, especially for developing countries; appropriate prevention and management strategies are needed to reduce this burden.