Background Clival infiltration is frequently seen in nasopharyngeal carcinoma (NPC) and the resultant bone marrow signal changes (BMSC) can persist even after complete tumor response to the radiation therapy (RT). The differentiation of those residual BMSC from recurrent/persistent disease may be challenging. We performed serial analysis of the clival BMSC after RT, to define an expected temporal evolution of those signal changes during the follow-up. Materials and methods Serial MRI studies of 50 NPC patients (with or without initial clival infiltration) who had undergone RT were retrospectively examined. Abnormal clival BMSC and contrast enhancement (CE) were evaluated on each follow-up scan. Duration of BMSC/CE was correlated with the degree of baseline clival involvement (BCID), RT dose, and primary mass volume (PMV). Results Clival BMSC persisted without any evidence of recurrence, for a mean of 66.5 (max. 137) months (with accompanying CE for up to 125 months) in 26 patients with clival infiltration at diagnosis. Duration of BMSC and CE showed statistical correlations with PMW (p < 0.05), but not with RT dose or BCID. The rate of recurrence in clivus was 14%. New clival lesions that occurred within the first 12 months after RT (in six patients) did not develop recurrence suggesting radiation osteitis (12%). Conclusion After RT, residual clival medullary signal change/enhancement is seen in most NPC patients and can persist even years without recurrence.