Abstract: Objective: To investigate factors associated with iodine uptake in abdominal organs using dual-source dual-energy computed tomography (CT) and to provide evidence for optimizing contrast-enhancement protocols to improve the stability of iodine uptake. Methods: In this prospective study, patients who underwent contrast-enhanced abdominal CT at our institution between July and October 2025 were enrolled. All participants underwent imaging using a fixed iodine contrast-agent injection protocol on a dual-source dual-energy CT scanner. Portal venous phase iodine maps were reconstructed for analysis. Data collected included age, sex, height, weight, medical history (coronary heart disease, hypertension, diabetes mellitus, smoking history, and alcohol abuse history), and radiation exposure. Iodine uptake was measured in the liver, pancreas, spleen, and kidneys. Body mass index (BMI), size-specific dose estimate (SSDE), and effective dose were calculated. Linear regression analysis was performed to evaluate associations between clinical variables and iodine uptake in abdominal organs. Results: A total of 232 patients were included, of whom 132 (56.90%) were male. The median (interquartile range IQR) age was 63.00 (51.00–71.00) years, and the median BMI was 22.89 (20.83–25.01) kg/m². Among these patients, 27 (11.64%) had coronary heart disease, 87 (37.5%) had hypertension, 45 (19.40%) had diabetes mellitus, 36 (15.52%) had a history of smoking, and 19 (8.19%) reported alcohol abuse. The median SSDE and effective dose were 6.11 (5.39–7.27) mGy, and 3.18 (2.60–4.00) mSv, respectively. Female sex was associated with significantly higher iodine uptake in the liver, pancreas, spleen, and kidneys than male sex (all P≤0.006, β=4.016–13.286). Higher BMI was associated with lower iodine uptake in all organs examined (all P < 0.001; β=−1.978 to −1.438 per 1 kg/m² increase in BMI). Older age was associated with higher iodine uptake in the pancreas, spleen, and kidneys (all P < 0.001; β=0.195–0.405 per year). Coronary heart disease (all P≤0.032; β=−10.46 to −5.351) and diabetes mellitus (all P≤0.045; β=−9.537 to −3.758) were associated with lower iodine uptake in the pancreas, spleen, and kidneys. Hypertension, smoking history, and alcohol abuse history were not significantly associated with iodine uptake in any abdominal organ (all P≥0.104). Conclusions: Both diabetes mellitus and coronary heart disease are independently associated with abdominal organ diseases and may increase the risk of disease onset, severe progression, and poor prognosis. After adjusting for sex, age, BMI, comorbidities, smoking history, and alcohol abuse history, diabetes mellitus and coronary heart disease remained associated with iodine uptake in abdominal organs.