The highly selective RET inhibitor selpercatinib showed high efficacy and favorable toxicity profile in treating patients with RET-altered thyroid cancer (TC). Erectile dysfunction (ED) is a common adverse event observed in patients with advanced cancers. This study aims to evaluate the occurrence of ED in TC patients treated with selpercatinib. In a multi-center retrospective cohort study, we investigated the prevalence of ED in 25 male patients treated with selpercatinib for advanced TC. The management of ED was also examined. 18/25 (78.3%) patients presented ED after starting selpercatinib treatment. However, only 2/18 (11.1%) spontaneously reported ED, while 16/18 (88.9%) reported ED only after specific questioning. Ten patients started treatment with phosphodiesterase-5 inhibitors (PDE-5i) with a significant improvement of ED. In this study, we observed that ED was not infrequently reported among men treated with selpercatinib for RET-altered TC. We believe that clinicians should actively inquire about ED in such patients at it may be underreported but may be amenable to treatment.