Background: Many middle-aged and older persons have more than one chronic condition. Thus, it is important to synthesise the effectiveness of interventions across several comorbidities. The aim of this systematic review was to summarise current evidence regarding the effectiveness of Tai Chi in individuals with four common chronic conditions-cancer, osteoarthritis (OA), heart failure (HF) and chronic obstructive pulmonary disease (COPD). Methods: 4 databases (MEDLINE, EMBASE, CINAHL and SPORTDiscus) were searched for original articles. Two reviewers independently screened the titles and abstracts and then conducted full-text reviews, quality assessment and finally data abstraction. 33 studies met the inclusion criteria. Meta-analyses were performed on disease-specific symptoms, physiological outcomes and physical performance of each chronic condition. Subgroup analyses on disease-specific symptoms were conducted by categorising studies into subsets based on the type of comparison groups. Results: Meta-analyses showed that Tai Chi improved or showed a tendency to improve physical performance outcomes, including 6-min walking distance (6MWD) and knee extensor strength, in most or all four chronic conditions. Tai Chi also improved disease-specific symptoms of pain and stiffness in OA. Conclusions: The results demonstrated a favourable effect or tendency of Tai Chi to improve physical performance and showed that this type of exercise could be performed by individuals with different chronic conditions, including COPD, HF and OA.