Cardiac biomarkers play an important role in the diagnosis of cardiovascular disease. Elevated levels can be seen in the context of strenuous exercise. We studied this phenomenon in senior endurance runners. We included 185 participants (61.1 ± 5 years; 29% women) at a 30-km cross-country race who were self-reportedly in excellent health. Before and after the race, the creatinine, N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T were analyzed, and participation in the number of previous races and the race duration were recorded. NT-proBNP increased from 53 ng/L (interquartile range 31 to 89) to 121 ng/L (interquartile range 79 to 184) and troponin T from undetectable to 0.01 μg/L (interquartile range 0.01 to 0.04). The independent predictors of a large NT-proBNP increase were (1) greater levels present at baseline, (2) a greater increase in creatinine (both p <0.001), (3) older age (p = 0.01), and (4) a longer race duration (p <0.05). Troponin T elevation was independently predicted by (1) older age (p = 0.01), (2) a greater increase in creatinine, and (3) participation in fewer previous races (both p <0.05). Of the 15 runners with an elevated (>194 ng/L) baseline NT-proBNP level (8.1% of 185), 4 were found to have serious cardiovascular disease (2.2% of whole sample). Of these 4 patients, 1 died from sudden cardiac death within months after the race. In conclusion, biomarker elevation occurs commonly in senior runners. A high baseline NT-proBNP is predictive of a large release during exercise, suggesting that the factors that control the at rest levels also determine its release with exertion. Troponin T elevation was seen in less-experienced participants. A small group of very ill runners were identified by NT-proBNP analysis.