Purpose: To determine whether the prevalences of various systemic conditions in participants of the MacTel Project Natural History Observation (NHO) Study differ from the corresponding prevalences in the general population. Methods: This report compares the prevalence of systemic disease in participants of the NHO Study with age- and sex-matched controls from three population-based studies from the US, the Netherlands and Australia. Bootstrap simulations were used to evaluate the impact and reliability of the computed statistics. Results: We identified a number of systemic conditions that appear to be more prevalent in cases with macular telangiectasia (MacTel) Type 2 than in the general population that were matched for age and sex with the MacTel cases. Patients with MacTel Type 2 had significantly increased prevalence of diabetes mellitus, higher prevalence of obesity, hypertension and history of cardiovascular disease, compared to their same-aged peers in generally older communities. Conclusion: Systemic disease associated with MacTel Type 2 may help to improve understanding of possible causes of MacTel Type 2. It is hoped that future studies will help to improve our understanding of the pathogenesis of the condition and lead to potential treatments for this ocular disease.