Introduction: Endoscopic advancements in stenting and tissue plication have proven to be viable alternatives to surgical management of esophageal perforations and are increasingly being used in clinical practice. We aim to assess the efficacy and outcome of different endoscopic treatment modalities in patients with esophageal perforations. Methods: We performed a retrospective analysis of patients with esophageal perforations from an endoscopic database since 2007. Patients with esophageal fistula, stricture, or stenosis were excluded. Patients were categorized into four treatment groups: primary closure (endoscopic suturing), primary bypass (stenting), combination (suturing defect and stenting), and conservative therapy (NPO, trans-nasal feeding tubes). Baseline demographics, patient characteristics, and treatment modality outcomes were collected. Predictors of success were identified using logistic regression. Results: 95 patients (mean age 64 ±15, 67% male) with esophageal perforations were included. The most common etiology was iatrogenic after dilatations or endoscopic myotomy (40%). 64% of perforations were in the distal esophagus. Regardless of strategy employed, 49% of patients had successful endoscopic repair of perforation. Only 7 patients required subsequent operative intervention. The combination approach achieved the greatest clinical success (66%), defined as no need for surgical intervention, when compared to the other modalities (primary bypass 35%, closure 57%, and conservative 25%, p=0.05). Patients with concomitant systemic inflammatory response syndrome had greater clinical success if they were treated with combination approach compared to primary bypass approach (18% vs. 64%, p=0.01). If the perforation was greater than or equal to 20mm, combination therapy had greater clinical success compared to primary bypass approach (0% vs. 50%, p=0.04). Early stent migration was associated with greater need for rescue surgery (p=0.02). (Table) Conclusion: Esophageal perforations can be managed effectively with endoscopic therapy. Larger, prospective trials are needed to clarify ideal individualized endoscopic strategies. Patients with systemic inflammatory response and/or perforation ≥20 mm are managed most effectively with combination therapy. Table 1. - Demographics, Presentation and Outcomes by Treatment Group Variables (%) All (n=95) Primary bypass (n=43) Primary closure (n=12) Combination(n=29) Conservative(n=11) Demographics All Primary bypass (n=43) Primary closure (n=12) Combination (n=29) Conservative (n=11) p-value Age (± SD) 63 ±14 66 ±13 61 ±13 61 ±15 64 ±15 0.23 Sex (Male) 64(67) 16(70) 10 (83) 19(65) 7(63) 0.61 History of EC 14 (16) 6(26) 1(8.3) 3(10) 2(18) 0.31 History of Radiotherapy 15 (19) 6(26) 0(0) 4(14) 2(18) 0.245 Diabetes 14(15) 2(9) 7 (43) 3(10) 2(18) 0.686 Hypertension 48(51) 12(52) 7(58) 13(45) 5(46) 0.927 Sleep apnea 16(17) 5(22) 2(17) 5(17) 0(0) 0.45 Site of Perforation Proximal 4(9.3) 0 2(6.9) 6(54.5) Middle 7(6.3) 3(25.0) 7(24.1) 0 Distal 29 (67.4) 8(66.7) 20(69.0) 5(45.5) Etiology of perforation SpontaneousIatrogenicFood impactionAnastomotic leakEsophageal cancer Boerhaave syndrome 7(16.3)22(51.2)2(4.7) 4(9.3) 2(4.7)6(14.0) 1(8.3)9(75.0)1(8.3) 0 01(8.3) 021(72.4)2(6.9) 3(10.3) 01(3.4) 2 (18.2)7(63.6)1(9.1) 0 01(9.1) Symptoms at time of diagnosis DysphagiaChest painAbdominal painFeverOther 10(23.3)11(25.6)1(2.3) 4(9.3)10(23.3) 1(8.3)4(33.3)0 1(8.3)2(16.7) 4(13.8)4(13.8)1(3.4) 5(17.2)8(27.6) 4(36.4)1(9.1)1(9.1) 02(18.2) Outcomes by Treatment Group Pittsburgh Perforation Severity Score (n=47) 3.17 ±2.1 3.59 ±2.2 2.5±2.0 2.72±1.8 3.45±2.25 0.225 Operative intervention required 7(5.7) 2(4.7) 1(8.3) 3(10.3) 1(9.1) 0.95 Mortality 9(7.4) 4(9.3) 0 3(10.3) 2(18.2) 0.652 SIRS 44(36.1) 19(44.2) 4(33.3) 16 (55.2) 5(45.5) 0.635 Stent migration 11 10(23.3) 0 2(6.9) 0 0.182 LOS* (days) 16±15 19 ±15 11±10 18±19 7.9±7.0 0.123 LOF* (months) 4.6±4.1 4.25±1.5 6±8.8 3.5±2.1 9.3±6.4 0.07 *LOS – Length Of Stay In The Hospital; LOF - Time From Diagnosis To Last-Follow Up; SIRS - Systemic Inflammatory Response Syndrome)