126 Background: Leaks from intrathoracic esophagogastric anastomosis are thought to be associated with higher rates of morbidity and mortality than leaks from cervical anastomosis. We challenge this assumption, and hypothesize that there is no significant difference in mortality based on the position of the esophagogastric anastomosis. Methods: A systematic literature search was conducted using PubMed and Embase databases on all studies published between January 2000 and June 2015 comparing transthoracic (TTE) and transhiatal (THE) esophagectomies. Studies that used alternate reconstruction approaches were excluded. Outcomes analyzed were leak rate, leak-associated mortality, overall 30-day mortality, and overall morbidity. Meta-analyses were performed using Mantel Haenszel statistical analyses on studies that reported on leak rates of both approaches. Nominal data are presented as frequency and interquartile range (IQR); measures of the association between treatments and outcomes are presented as odds ratio (OR) with 95% confidence interval (CI). Results: Twenty-one studies (including 3 randomized controlled trials) were included comprising of 7167 patients (54% TTE). THE approach yields a higher anastomotic leak rate (12%; IQR: 11.6% - 22.1%) than TTE (9.8%; IQR: 6.0% - 12.2%) (OR: 1.83 [0.34-06.92]), without any difference in leak-associated mortality (7.1% TTE vs. 4.6% THE; OR: 1.83, [0.39-8.52]). There was no difference in overall 30-day mortality (3.9% TTE vs. 4.3% THE; OR: 0.86, [0.66-1.13]) and morbidity (59.0% TTE vs. 66.6% THE; OR: 0.76, [0.37-1.59]). Conclusions: Transthoracic esophagectomy is associated with a lower leak rate and does not result in higher morbidity or mortality than transhiatal esophagectomy. The previously assumed higher rate of transthoracic leak-associated mortality is overstated, thus allowing surgeon discretion and other factors to influence the choice of intrathoracic versus cervical esophagogastric anastomosis.