Background: Although several large series have reported on EUS-guided transgastric and transduodenal drainage of peripancreatic fluid collections (PFCs), only commentary on individual cases has been presented on EUS-guided transesophageal drainage of PFCs. Objective: To evaluate the technical success and safety of EUS-guided transesophageal drainage of PFCs. Design: Observational study. Setting: Tertiary academic referral center. Patients: This study involved 3 consecutive patients referred for EUS-guided transesophageal drainage of PFCs over a 3-year period. Interventions: The PFCs were accessed via the transesophageal route under EUS-guidance by using a 19-gauge needle. After a 0.035-inch guidewire was passed into the PFC, and the transmural tract was dilated to 6 mm, a transmural stent and/or drainage catheter was deployed. Main Outcome Measurements: Evaluation of the technical and treatment success and safety profile of EUS-guided transesophageal drainage of PFCs. Results: Three male patients (mean age 57.8 years [range 49-75 years]) underwent EUS-guided transesophageal drainage of PFCs (2 pseudocyst, 1 abscess) over a 3-year period. The etiology of the PFC was alcohol abuse in 2 patients and postsurgical in 1. The mean size of the PFCs was 7 cm (range 6-8 cm) in its largest dimension. The procedures were technically successful in all 3 patients, and no complications were encountered. All 3 patients had a successful treatment outcome. At a mean follow-up period of 24 months (range 12-36 months), all patients were doing well, without any evidence of PFC recurrence. Limitation: Small number of patients. Conclusions: In experienced hands, EUS-guided transesophageal drainage of PFCs is technically feasible and safe and is associated with favorable clinical outcomes. A long-term follow-up with larger numbers of patients is required to determine whether the procedure could be an effective alternative to surgical cyst-enterostomy or percutaneous drainage techniques. © 2009 American Society for Gastrointestinal Endoscopy.