BACKGROUND: Zenker's diverticulum (ZD) is a rare condition with a reported prevalence of 0.01% to 0.11% in the general population. Endoscopic treatment consists of the division of the septum between the diverticulum and the esophagus, within which the cricopharyngeal muscle is contained. Diathermic monopolar current, argon plasma coagulation, and laser have been used to incise the muscular septum with satisfactory results. The main limitation of endoscopic treatment is the occurrence of complications. Perforation and hemorrhage are reported in as many as 23% and 10% of patients, respectively. OBJECTIVE: The aim of this study was to use the technique of endoscopic diverticulotomy by using a harmonic scalpel in patients with ZD and to demonstrate the feasibility of using flexible and rigid devices in ZD treatment. DESIGN: Case series study. Standard protocol was used for patient management, endoscopic procedure, and data collection. SETTING: Single endoscopist demonstrating preliminary results. PATIENTS: Five patients (4 men; median ± standard deviation [SD] age 69.6 ± 9.06 years, range 59-83 years) with ZD were treated with this technique. All patients reported dysphagia and halitosis. The diagnosis was based on clinical, endoscopic, and radiographic findings. INTERVENTIONS: All patients received general anesthesia and were placed in the left lateral position. A standard videogastroscope (9.8 mm) and a stiff guidewire were used to insert and achieve an adequate exposure of the ZD septum. The septum was divided using a harmonic scalpel under thin endoscope (5.2 mm) visualization through a soft diverticuloscope. MAIN OUTCOME MEASUREMENT: Feasibility of an endoscopic technique by using rigid and flexible devices to treat ZD. RESULTS: Four patients (80%) were successfully treated in 1 session. The median ± SD size of the diverticulum was 3.6 ± 0.89 cm (range 3-5 cm). Median ± SD procedure time was 17.33 ± 2.33 minutes (range 15-20 minutes) in 6 procedures. No hemorrhage or perforation occurred. One patient (20%) required a second session to complete dissection of the ZD septum. All patients demonstrated improvement of dysphagia score after treatment. LIMITATIONS: Small case series design. CONCLUSIONS: Endoscopic treatment of ZD by harmonic scalpel through a soft diverticuloscope was feasible and effective in this small case series. Larger studies are warranted to further evaluate this technique.