Plasma adiponectin is inversely associated with the risk of coronary heart disease in healthy people. However, adiponectin and BNP (B-type natriuretic peptide) are both known to be positively associated with a risk of poor outcome, and with each other, in ACS (acute coronary syndrome) patients. Serial changes in plasma adiponectin and BNP following ACS have not been assessed previously, and may clarify these apparently paradoxical associations. In the present study, adiponectin, BNP, classical risk markers and clinical parameters were measured in plasma from 442 consecutive ACS patients in an urban teaching hospital, with repeat measures at 7 weeks (n=338). Patients were followed-up for 10 months. Poor outcome was defined as mortality or readmission for ACS or congestive heart failure (n=90). In unadjusted analysis, the change in adiponectin (but not baseline or 7-week adiponectin) was significantly associated with the risk of an adverse outcome {odds ratio (OR), 5.42 [95% CI (confidence interval), 2.78-10.55]}. This association persisted after adjusting for classical risk factors and clinical markers, but was fully attenuated by adjusting for the 7-week BNP measurement [OR, 1.13 (95% CI, 0.27-4.92)], which itself remained associated with risk [OR, 5.86 (95% CI, 1.04-32.94)]. Adiponectin and BNP positively correlated at baseline and 7 weeks, and the change in both parameters over 7 weeks also correlated (r=0.39, P<0.001). In conclusion, increases in plasma adiponectin (rather than absolute levels) after ACS are related to the risk of an adverse outcome, but this relationship is not independent of BNP levels. The results of the present study allude to a potential direct or indirect relationship between adiponectin and BNP post-ACS which requires further investigation.