Background Although tafamidis treatment improves prognosis in patients with wild‐type transthyretin amyloid cardiomyopathy, an optimal surrogate marker monitoring its therapeutic effect remains unclear. This study investigated the association between changes in cardiac biomarkers, high‐sensitivity cardiac troponin T (hs‐cTnT) and B‐type natriuretic peptide (BNP) during the first year after tafamidis treatment and clinical outcomes. Methods and Results In 101 patients with wild‐type transthyretin amyloid cardiomyopathy receiving tafamidis at our institution, change in cardiac biomarkers from baseline to 1 year after tafamidis administration and its association with composite outcomes (composite of all‐cause death and hospitalization attributable to heart failure) was assessed. During the follow‐up period (median, 17 months), 16 (16%) patients experienced composite outcomes. The hs‐cTnT level significantly decreased at 1 year after tafamidis treatment, unlike the BNP level. The frequencies of increased hs‐cTnT and BNP levels were significantly higher in those with composite outcomes than in those without (44% versus 15%; P =0.01). Kaplan‐Meier survival analysis showed that patients in whom both hs‐cTnT and BNP levels increased at 1 year after tafamidis had a higher probability of composite outcomes compared with those with decreased hs‐cTnT and BNP levels (log‐rank P <0.01). Cox regression analysis identified increased hs‐cTnT and BNP levels at 1 year after tafamidis administration as an independent predictor of higher cumulative risk of composite outcomes. Conclusions Deterioration in cardiac biomarkers during the first year after tafamidis treatment predicted a worse prognosis, suggesting the utility of serial assessment of cardiac biomarkers for monitoring the therapeutic response to tafamidis in patients with wild‐type transthyretin amyloid cardiomyopathy.