Breast lumpectomy is usually performed under general or local anesthesia. To the best of our knowledge, whether conscious sedation with intranasal dexmedetomidine and local anesthesia is an effective anesthetic technique has not been studied. Thus, the present study aimed to investigate the effectiveness of conscious sedation with intranasal dexmedetomidine combined with local anesthesia in breast lumpectomy, and to identify its optimal dose. A prospective randomized, double-blinded, placebo-controlled, single-center study was designed, and patients undergoing breast lumpectomies were recruited based on the inclusion and exclusion criteria. All patients were randomly allocated to four groups: i) Local anesthesia with 0.9% intranasal saline (placebo); local anesthesia with ii) 1 µg.kg-1 ; iii) 1.5 µg.kg-1 ; or iv) 2 µg.kg-1 intranasal dexmedetomidine. The sedation status, pain relief, vital signs, adverse events, and satisfaction of patient and surgeon were recorded. Patients in the three dexmedetomidine groups were significantly more sedated and experienced less pain compared with the placebo group 45 min after intranasal dexmedetomidine administration and during 30 min in the post-anesthesia care unit. Patients in the 1.5 µg.kg-1 group were more sedated compared with the 1 µg.kg-1 group (without reaching statistical significance), whereas the 1.5 µg.kg-1 group exhibited a similar level of sedation 45 min after intranasal dexmedetomidine administration compared with the 2 µg.kg-1 group. In addition, patients in the 1 and 1.5 µg.kg-1 group experienced no adverse hemodynamic effects. Patient and surgeon satisfaction were greater in the 1.5 µg.kg-1 group compared with the 1 and 2 µg.kg-1 groups. Taken together, the results of the present study suggested that conscious sedation with intranasal dexmedetomidine and local anesthesia may be an effective anesthetic for breast lumpectomy surgery, and that the optimal dose for intranasal dexmedetomidine administration may be 1.5 µg.kg-1 , as it resulted in good sedation and patient satisfaction without adverse effects.