Abstract Objectives Patient-tailored contrast delivery protocols strongly reduce the total iodine load and in general improve image quality in CT coronary angiography (CTCA). We aim to use machine learning to predict cases with insufficient contrast enhancement and to identify parameters with the highest predictive value. Methods Machine learning models were developed using data from 1,447 CTs. We included patient features, imaging settings, and test bolus features. The models were trained to predict CTCA images with a mean attenuation value in the ascending aorta below 400 HU. The accuracy was assessed by the area under the receiver operating characteristic (AUROC) and precision-recall curves (AUPRC). Shapley Additive exPlanations was used to assess the impact of features on the prediction of insufficient contrast enhancement. Results A total of 399 out of 1,447 scans revealed attenuation values in the ascending aorta below 400 HU. The best model trained using only patient features and CT settings achieved an AUROC of 0.78 (95% CI: 0.73–0.83) and AUPRC of 0.65 (95% CI: 0.58–0.71). With the inclusion of the test bolus features, it achieved an AUROC of 0.84 (95% CI: 0.81–0.87), an AUPRC of 0.71 (95% CI: 0.66–0.76), and a sensitivity of 0.66 and specificity of 0.88. The test bolus’ peak height was the feature that impacted low attenuation prediction most. Conclusion Prediction of insufficient contrast enhancement in CT coronary angiography scans can be achieved using machine learning models. Our experiments suggest that test bolus features are strongly predictive of low attenuation values and can be used to further improve patient-specific contrast delivery protocols. Key Points • Prediction of insufficient contrast enhancement in CT coronary angiography scans can be achieved using machine learning models. • The peak height of the test bolus curve is the most impacting feature for the best performing model.