Abstract Purpose The purpose of this study was to assess the diagnostic accuracy of T1-weighted and T2-weighted contrasts generated by the MR data postprocessing software SyMRI (Synthetic MR AB, Linköping, Sweden) for neonatal brain imaging. Methods In this study 36 cases of neonatal MRI were retrospectively collected, which included T1-weighted and T2-weighted sequences as well as multi-dynamic multi-echo (MDME) sequences. Of the 36 neonates 32 were included in this study and 4 neuroradiologists independently assessed neonatal brain examinations on the basis of conventional and SyMRI-generated T1-weighted and T2-weighted contrasts, in order to determine the presence or absence of lesions. The sensitivity and specificity of both methods were calculated and compared. Results Compared to conventionally acquired T1 and T2-weighted images, SyMRI-generated contrasts showed a lower sensitivity but a higher specificity (SyMRI sensitivity 0.88, confidence interval (CI): 0.72–0.95; specificity 1, CI: 0.89–1/conventional MRI: sensitivity: 0.94, CI: 0.80–0.98; specificity: 0.94, CI: 0.80–0.98). Conclusion The T1-weighted and T2-weighted images generated by SyMRI showed a diagnostic accuracy comparable to that of conventionally acquired contrasts. In addition to semiquantitative imaging data, SyMRI provides diagnostic images and leads to a more efficient use of available imaging time in neonatal brain MRI.