Abstract Objectives We aimed to assess extracellular volume (ECV) through non-gated, contrast-enhanced computed tomography (CT) before and after radiation therapy (RT) in patients with esophageal cancer (EC). Materials and methods EC patients who had undergone CT before and after RT were retrospectively assessed. Patients with preexisting cardiovascular disease or with heavily artifacted CT were excluded. ECV was calculated using density values for the myocardial septum and blood pool. Data were reported as mean and standard deviation or median and interquartile range according to their distribution; t test or Wilcoxon and Pearson r or Spearman ρ were subsequently used. Results Twenty-one patients with stage ≥ IB EC, aged 64 ± 18 years, were included. Mean and maximum RT doses were 21.2 Gy (16.9–24.1) and 42.5 Gy (41.8–49.2), respectively. At baseline (n = 21), hematocrit was 39% ± 4%, ECV 27.9% ± 3.5%; 35 days (30–38) after RT (n = 20), hematocrit was 36% ± 4%, lower than at baseline (p = 0.002), ECV 30.3% ± 8.3%, higher than at baseline (p = 0.081); at follow-up 420 days (244–624) after RT (n = 13), hematocrit was 36% ± 5%, lower than at baseline (p = 0.030), ECV 31.4% ± 4.5%, higher than at baseline (p = 0.011). No patients showed signs of overt cardiotoxicity. ECV early after RT was moderately positively correlated with maximum RT dose (ρ = 0.50, p = 0.036). Conclusions In EC patients, CT-derived myocardial ECV was increased after RT and may thus appear as a potential early biomarker of cardiotoxicity.