OBJECTIVES: Minimally invasive parathyroidectomy (MIP) is generally performed under general anesthesia. This study evaluates the efficacy and safety of MIP performed under intravenous sedation with local anesthesia. STUDY DESIGN: Historical cohort study. SUBJECTS: One hundred eighty-six consecutive patients undergoing MIP using sedation with local anesthesia. METHODS: Two different targeted approaches were used to achieve good exposure with minimal retraction, which allows the procedure to be performed with little discomfort. In all patients, an adenoma was localized preoperatively and its depth mapped by sestamibi scan with single-photon emission computed tomography and/or ultrasound. A midline anterior approach was used for inferior glands that were superficially located. A lateral approach was used for glands that were located posteriorly or superiorly. RESULTS: MIP was successfully completed under local/sedation in 177 patients; 167 were discharged the same day. Complications include two pneumothorax, one small hematoma, and one transient vocal cord paralysis. CONCLUSIONS: By using a targeted approach, MIP can be safely performed under local anesthesia in appropriately selected patients.