BACKGROUND AND AIMS: Carcinoma of the esophagus is an aggressive cancer with a high failure rate after combined local and systemic treatment modalities. One of the factors that could influence the high rate of locoregional persistence is hypoxia. Hypoxic cancers are known to be more aggressive and less responsive to chemo- and radiotherapy. We investigated the effect of several factors on overall survival and several surrogate markers of hypoxia on survival in squamous-cell esophageal cancer. PATIENTS AND METHODS: We conducted a retrospective analysis of 41 curatively treated patients with squamous-cell esophageal cancer: 30 received combined radio- and chemotherapy (cisplatin and 5-FU) and 11 radiotherapy alone. Cox regression analysis was performed to study the effect of several factors on overall survival. RESULTS: Significantly better survival was shown only in patients who were younger, received more cycles of chemotherapy, or had more proximal tumors or less advanced T stage but not for possible clinical surrogate markers for hypoxia, such as levels of hemoglobin before and during treatment or smoking. CONCLUSION: We found no clinical evidence that hypoxia plays a role in survival with squamous-cell esophageal cancer. Number of chemotherapy cycles was, independently of age, predictive of survival. Measurements of in vivo tumor oxygenation could further help in determining the role of tumor hypoxia in esophageal cancer.