Many centers use botulinum toxin for chemical pyloroplasty in minimally invasive esophagectomies as prophylaxis against delayed gastric emptying. No previous studies have compared botulinum toxin injection with no pyloric intervention for patients treated with a combined laparoscopic and thoracoscopic approach. The authors hypothesized that chemical pyloroplasty does not improve outcomes for these patients. The study investigated patients undergoing minimally invasive esophagectomies from September 2009 to June 2015. Delayed gastric emptying was defined as inability to tolerate a soft diet by postoperative day 10, as corroborated by esophagram, upper endoscopy, or both. Data were compared using Student's t test, χ 2 analysis, and Mann-Whitney U test where appropriate. The study identified 71 patients treated with minimally invasive esophagectomy: 35 patients with chemical pyloroplasty treated from September 2009 to January 2014 and 36 patients without pyloric intervention from February 2014 to June 2015. The groups were statistically similar in age, gender distribution, T stage, percentage of patients receiving neoadjuvant therapy, body mass index, preoperative weight loss, preoperative serum albumin, and preoperative placement of feeding tubes (all p>0.05). The overall incidence of delayed gastric emptying was low in both groups: 8.6% (3/35) of the patients with chemical pyloroplasty versus 5.6% (2/36) of the patients with no pyloric intervention (p=0.62). The two groups also did not differ significantly in the development of aspiration pneumonia or the need for pyloric intervention. In a well-matched cohort study with a historical control group, use of botulinum toxin for chemical pyloroplasty in minimally invasive esophagectomies was not associated with improved outcomes related to the pylorus versus no pyloric intervention. Although preliminary, these data suggest that chemical pyloroplasty is not necessary in minimally invasive esophagectomy.