Purpose: Comorbidity is highly prevalent in osteoarthritis, although the origin of this is not well understood. The presence of multiple symptomatic joint involvement in osteoarthritis, and noted associations between obesity and osteoarthritis in non-weight bearing joints, implicates osteoarthritis as a likely systemic disorder. Lung disease is prevalent in osteoarthritis populations and also has been associated with systemic factors. Our purpose is to investigate the association between the extent of symptomatic joint involvement in osteoarthritis and prevalent lung disease. Methods: Patients with end-stage hip and knee osteoarthritis were recruited from an orthopaedic clinic in 2010–2012. Patient questionnaires captured symptomatic joints, comorbidities (lung disease, heart disease, diabetes, and high blood pressure), height and weight, smoking status, functional limitations (Western Ontario McMaster University Osteoarthritis Index physical function subscale) and demographic characteristics. Bivariate analysis tested trends in lung disease prevalence by symptomatic joint count categories (1; 2–4; and 5+) stratified by body mass index (BMI: normal (18.5≤BMI<25); overweight (25≤BMI<30); obese (≥30)). Logistic regression analyses evaluated the association between symptomatic joint count (continuous) and lung disease, adjusting for assessed other study measures. Results: Study sample: 913 (469 knees and 444 hips). Mean age was 64 years, 44% male. Lung disease was reported by 9.5%. Mean symptomatic joint count was 4.4 (range: 1–20); almost 40% reported ≥5 symptomatic joints. Comparing individuals reporting lung disease with those who did not, those reporting lung disease had significantly higher mean BMI (mean ± SD: 33.2 ± 8.0 vs 29.4 ± 6.2); more previous/current smokers 41.4% vs 23.6%, greater comorbidity (significantly more with heart disease, diabetes, and high blood pressure), and greater symptomatic joint count (mean ± SD: 6.2 ± 4.4 vs 4.2 ± 3.2). A statistically significant increasing trend in lung disease prevalence was observed with joint count categories (1; 2–4; 5+) within BMI categories. Within the normal BMI group, lung disease prevalence increased from 2.1% to 9.5% (p=0.042), within the overweight group from 4.1% to 9.4% (p=0.016) and within the obese group from 9.3% to 20.5% (p=0.007). Logistic regression showed, adjusted for study covariates, each numerical increase in symptomatic joint count was associated with a 7% (OR: 1.07, 95% CI: 1.01, 1.14) increased likelihood of reporting lung disease. Other independent predictors of lung disease were previous/current smoker (OR: 2.64, 95% CI: 1.32, 4, 5.26), reporting diabetes (OR: 2.37, 95% CI: 1.28, 4.40) and having functional limitations (OR: 1.03, 95% CI: 1.01, 1.06). Males were significantly less likely to report lung disease than females (OR: 0.42, 95% CI: 0.23, 0.75). Conclusions: Findings suggest that ‘generalized’ osteoarthritis may reflect a more systemic osteoarthritis phenotype. This may have important implications for the medical treatment and management of osteoarthritis, suggesting that the extent of joint involvement, and the presence or risk of comorbidity, should be considered in patient education, in choice(s) of treatment and management strategies, and in osteoarthritis research.