The present study employed novel echocardiographic tools and cardiac markers to obtain a greater understanding of the aetiology and time course of altered cardiac function and cardiac damage following prolonged exercise and, in particular, the possible role of transient ischaemia within these phenomena. Fourteen runners in the 2004 London Marathon were assessed pre-, immediately post-, 1 h post- and 24 h postcompletion of the race. Left ventricular function was examined echocardiographically using 2-D, M-mode, tissue Doppler imaging and flow propagation velocity (Vp). Venous blood samples were analysed for N-terminal pro-B-type natriuretic peptide (proBNP), cardiac troponin T (cTnT) and ischaemia-modified albumin (IMA). Left ventricular (LV) diastolic filling was altered on completion of the race, as indicated by significant decreases in mean early to late diastolic myocardial wave (E′:A′) ratio and Vp (from 1.82 ± 0.9 to 1.32 ± 0.32, and from 67.5 ± 9.3 to 60.2 ± 8.2 cm s−1, respectively, P < 0.05), accompanied by an increase in proBNP (from 21.6 ± 11 to 47.08 ± 19.5 pg l−1, P < 0.05). The observed reduction in LV diastolic filling following completion of a marathon, unrelated to changes in heart rate or loading parameters, indicates an intrinsically mediated change in diastolic filling. Exercise-induced elevations in cTnT in nine individuals (range, 0.023–0.37 μg l−1) were indicative of minor cardiac damage. A significant reduction in IMA was observed after the marathon (from 63.68 ± 9.83 to 44.94 ± 16.13 Um l−1, P < 0.05), unrelated to the alterations in cardiac function, proBNP or cTnT. The absence of an elevation in IMA suggests that exercise-induced myocardial ischaemia did not occur and therefore could not explain the changes in cardiac function or biomarkers. Future studies in this area should investigate alternative diagnostic tools for the detection of transient ischaemia, and other potential mechanisms, in order to extend the understanding of this phenomenon.