An isthmocele, also known as a cesarean scar defect, is an emerging condition that typically affects women with a history of previous cesarean section, and its presence is a novel under-recognized cause of postmenstrual abnormal uterine bleeding and/or pelvic pain. The incidence of symptoms and their resolution after hysteroscopic surgery were evaluated prospectively in 120 consecutive isthmocele patients. Patients included only symptomatic premenopausal women. Transvaginal ultrasound and office hysteroscopy were used to diagnose isthmocele. Operative hysteroscopy was performed to correct the cesarean scar defect, and histologic findings were evaluated. Correction of an isthmocele via operative hysteroscopy was successful in all cases evaluated. Isthmoplasty resulted in the resolution of postmenstrual abnormal uterine bleeding and suprapubic pelvic pain in 80% of patients. In the remaining cases, 7% of patients had an improvement of symptoms, whereas 13% did not obtain any relief. Considering the recent diagnostic recognition of isthmoceles, we conclude that surgical treatment of this pathology by operative hysteroscopy may represent the best choice in symptomatic women because of its minimal invasiveness and beneficial therapeutic results.