Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, along with its implications for postoperative radiotherapy of brain tumors. Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the mean CTV (mean SD: −62.92 93.99 cc; P = 0.006) and GTV (mean SD: −21.08 36.04 cc; P = 0.014). These differences were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be −106.7% and −62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in the regions of peritumoral edema.