Objective To compare a fixed-volume contrast medium (CM) protocol with a combined total body weight (TBW) and body composition-tailored protocol in chest CT. Methods and materials Patients referred for routine contrast enhanced chest CT were prospectively categorised as normal, muscular or overweight. Patients were accordingly randomised into two groups; Group 1 received a fixed CM protocol. Group 2 received CM volume according to a body composition-tailored protocol. Objective image quality comparisons between protocols and body compositions were performed. Differences between groups and correlation were analysed using t-test and Pearson’s r. Results A total of 179 patients were included: 87 in Group 1 (mean age, 51 ± 17 years); and 92 in Group 2 (mean age, 52 ± 17 years). Compared to Group 2, Group 1 showed lower vascular attenuation in muscular (mean 346 Hounsfield unit (HU) vs 396 HU; p = 0.004) and overweight categories (mean 342 HU vs 367 HU; p = 0.12), while normal category patients showed increased attenuation (385 vs 367; p = 0.61). In Group 1, strongest correlation was found between attenuation and TBW in muscular (r = −.49, p = 0.009) and waist circumference in overweight patients (r = −.50, p = 0.005). In Group 2, no significant correlations were found for the same body size parameters. In Group 1, 13% of the overweight patients was below 250 HU (p = 0.053). Conclusion A combined TBW and body composition-tailored CM protocol in chest CT resulted in more homogenous enhancement and fewer outliers compared to a fixed-volume protocol. Advances in knowledge This is, to our knowledge, the first study to investigate the impact of various body compositions on contrast medium enhancement in chest CT.