This prospectively designed, clinical quality improvement project compared pain scores and opioid consumption between ultrasound-guided, erector spinae plane blocks (ESPB) and thoracic paravertebral blocks (PVB) in patients undergoing total bilateral mastectomies without reconstruction. Twenty-five patients were included in an enhanced recovery pathway and received an ESPB on one side and a PVB on the contralateral side. Numeric rating scores at rest and with movement for each side were recorded in the recovery room at 2, 6, 12, 24, and 48 hours and on days 3 to 7. There were no significant differences in the resting or movement-evoked pain scores between sides receiving ESPB or PVB at any time point up to day 7 after surgery. Both ESPB and PVB confer equal analgesic effects in patients undergoing mastectomies. ESPB provides an alternative to PVB in reducing postoperative pain in patients undergoing mastectomy as part of an enhanced recovery pathway.