Migration, urbanization, and change in socio-economic factors have potentially profound effects on heart disease in low-to-middle income countries.Chris Hani Baragwanath Hospital in Soweto, South Africa, provides health care to >1 million Africans. We systematically captured data from all de novo presentations of suspected heart disease (focusing on 'new' vs. historically prevalent forms) during 2006-2008. There were 3168 female (52 ± 18 years) vs. 2160 male (53 ± 17 years) cases. Overall, 999 (19%) presented with uncomplicated hypertension (n = 988) or type II diabetes, 1862 cases (35%) 'new' heart disease (1146 and 581 cases of hypertensive heart failure and coronary artery disease), and 2092 cases (39%) of historically prevalent heart disease (including 724 with primary valve disease and 502 idiopathic dilated cardiomyopathies). Level of education and non-communicable risk factors were important correlates of advanced disease. The rate of historically prevalent cases was higher in those aged 20-49 years (19-60 cases/100,000 population/annum) whilst being higher for "new" heart disease in those aged >50 years (155-343 cases/population/annum). Historically prevalent heart disease cases were younger [adjusted odds ratio (OR) 0.98, 95% 0.97-0.99 per year], more likely to be African (OR 4.59, 95% 2.76-7.60) while being less likely to originate from Soweto (OR 0.87, 95% 0.75-1.00) and be female (OR 0.67, 95% 0.49-0.92).Dynamic socio-economic and lifestyle factors characteristic of epidemiological transition appear to have positioned the urban, mainly African community of Soweto at the crossroads between historically prevalent and 'new' forms of heart disease.