The impact of target organ damage (TOD) clustering in hypertensive patients with established cardiovascular disease has not been clearly defined. Multicentre, observational and prospective study of 1054 consecutive patients with acute coronary syndromes (ACSs). The objective was describing the impact of TOD on first-year mortality. Ankle-brachial index (ABI), left ventricular hypertrophy and renal dysfunction were assessed during hospital stay. Hypertensive patients accounted for 80% of the cohort and had slightly higher mean age, higher prevalence of risk factors, previous cardiovascular disease and TOD. During follow-up, mean time 387.9 (7.2) days and median 382 (364.0-430.0) days, mortality rate tended to be higher in hypertensive patients (6.1 versus 3.5%; P=0.16). Cox regression survival analysis identified pathological ABI as the only TOD independently associated with mortality. When assessed globally, the presence of at least one TOD predicted mortality only in patients with hypertension and differences in mortality rate appeared very early in the follow-up. A linear increase in mortality rate was observed with the clustering of TOD: 2.0%, if no TOD was present, 7.6% in one TOD, 11.1% in two TODs and 20.0%, if three TODs were present. An increased risk in the combined end point of ischaemic events was observed in hypertensive patients without TOD (odds ratio (OR): 3.18; 95% confidence interval (CI): 1.31-7.70; P=0.01) and was still higher in patients with hypertension and TOD (OR: 4.61; 95% CI: 1.90-11.80; P<0.01). TOD predicts mortality and ischaemic events of hypertensive patients after ACS.