Previous researchers have focused upon the influence of postoperative complications upon prognosis from esophagectomy, with very little attention paid to the potential negative effects of complications during neoadjuvant therapy. The hypothesis under investigation in this study was that the prognosis after esophageal cancer surgery is negatively influenced by complications causing hospital admission during neoadjuvant therapy. Patients receiving neoadjuvant therapy and surgery for esophageal cancer between 1987 and 2010 were identified from a population-based nationwide Swedish cohort study and followed up until 2016. The association between hematological and nonhematological complications during neoadjuvant therapy and risk of short- and long-term mortality following surgery was analyzed using a multivariable Cox proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs). The HRs were adjusted for appropriate confounding variables.Among 587 patients, complications during neoadjuvant therapy requiring emergency hospitalization affected 65 (12%) patients. Hematological complications were associated with an increased 90-day overall mortality (HR = 5.60; 95% CI 1.27-24.75), particularly in subgroups of patients of tumor stage 0-II, adenocarcinoma, and radical and nonradical resection margins, and rendered increased 5-year disease-specific mortality specifically for esophageal adenocarcinoma (HR = 3.22; 95% CI 1.00-10.40). Occurrence of nonhematological complications was followed by an increase in 5-year mortality (HR = 2.35; 95% CI 1.15-4.81) in poor prognostic groups (tumor stage III-IV). There was no increased 5-year mortality following hematological or nonhematological complications in other subgroups of patients. Complications during neoadjuvant therapy may adversely impact short and long-term mortality in subgroups of patients with esophageal cancer receiving esophagectomy. Patient selection, optimization of neoadjuvant therapy, and timing of surgical resection, remain important areas for future development in the management of esophageal cancer.