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Background: We previously reported, in a pilot trial of 20 patients, the feasibility and safety of a new antireflux operation that combines components of the Nissen fundoplication with the Hill repair. This larger study evaluates the clinical and objective effectiveness of the repair in patients with paraesophageal hernia (PEH) and/or Barrett’s metaplasia (BE), where higher rates of recurrence have been reported with traditional repairs. Methods: An IRB approved, prospective study was performed on patients with symptomatic PEH or GERD with non-dysplastic BE. Manometry, EGD and 48-hour pH testing were obtained pre-operatively and 6 months post-operatively. Quality of life was measured with QOLRAD, GERD-HRQL and Dysphagia Severity Scores pre-operatively, at 6 weeks, 6 months and one year. Results: Fifty-five patients were enrolled in the study with 50 available for analysis. Thirty patients with PEH (mean hernia size = 6 cm), 15 with BE and 5 with both underwent Hybrid repair and were followed for a median of 12.8 months (6.4-39.1 months).There were no peri-operative mortalities. There were four major complications, including 1 intra-operative bougie perforation, 1 myocardial infarction, 1 intra-operative bleed and 1 early reoperation for esophageal obstruction. There was one clinical recurrence (2%), requiring reoperation at 3. 5 years, and two (4%) asymptomatic fundic herniations with an intact GEJ, all in the PEH group. No patient has resumed antisecretory medication. Control of preoperative symptoms was achieved in 96%. Two patients required post-operative dilatation for dysphagia, with resolution. Mean DeMeester scores improved from 51.4 to 8.5 (p < 0.001) and mean percent time pH < 4 decreased from 11.9% to 2.1% (p < 0.01). Abnormal DeMeester scores were noted in 4 asymptomatic patients (3 PEH and 1 BE). Lower esophageal sphincter pressures (LESP) increased from 16.2 to 22.8 mmHg (p < 0.03) with residual LESP increasing from 4.1 to 10.4 mmHg (p < 0.002). At 7.4 weeks post op, QOLRAD scores improved from 4.03 to 6.01 (p < 0.0001) and GERD-HQRL improved from 20.5 to 6.8 (p < 0.0001). At 9.3 months, QOLRAD improved from 4.07 to 6.63 (p < 0.0001) and GERD-HRQL improved from 20.0 to 4.6 (p < 0.0001). The Dysphagia Severity Score worsened at 7.4 weeks from 34.5 to 28.4 (p < 0.01) but then improved at long-term to 42.5 (p < 0.002). Conclusions: Laparoscopic Nissen-Hill hybrid is an effective repair for patients with PEH and/or BE. In this difficult group the clinical recurrence rate was 2% and no patient had resumed antisecretory medication at a mean follow up of 12.8 months. Long-term outcomes and comparison with other repairs are needed.