Molecular targeted therapies (TT) are the cornerstone of metastatic renal cell carcinoma (RCC) treatment. There is a paucity of data on the safety of the radiotherapy (RT)-TT association in a sequential or a concomitant setting. The aim of the present study is to retrospectively assess the safety of the RT-TT association. From 2006 to 2014, data from 84 consecutive patients treated with RT and TT for metastatic RCC were retrospectively collected. RT-TT sequential and concomitant associations were, respectively, defined by a time interval of more than five TT half-lives and less than or equal to five TT half-lives between the last TT administration and RT initiation. Toxicities in the fields of RT were assessed systematically. As many patients received several TT and RT courses, 136 RT-TT associations were analyzed, with 66 sequential and 70 concomitant schemes. RT was mainly delivered on bone (75%) and brain metastases (14.7%). TT were tyrosine kinase inhibitors (73.5%), mTOR inhibitors (19.8%), and monoclonal antibodies (6.7%). With a median follow-up of 9.5 months, whatever the sequence, no grade≥4 toxicity was reported. Two grade 3 toxicities were reported with sequential (3%) and concomitant (2.9%) RT-TT, respectively. Sequential or concomitant RT-TT associations in metastatic RCC do not seem to cause major toxicity.