Background. Nimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor. It was approved in Cuba for the indication of inoperable malignant tumors of the esophagus of epithelial origin. The purpose of this study was to evaluate the safety, overall and progression-free survival, clinical response, and quality of life, in adult patients with inoperable esophageal tumors of epithelial origin treated with nimotuzumab in a practical context. Material and Methods. The number of patients who developed adverse events was determined, and the frequency, seriousness, causality, and severity of these adverse events were determined. It also determined the median of survival and progression-free survival and rates at 12 and 24 months and the quality of life. Results. A total of 111 patients were included. The proportion of serious and related AE with the use of nimotuzumab was 1.3%. Most of the related AEs were mild and moderate, and the most frequent AEs were diarrhea, chills, and tremors. New diagnosed patients who received nimotuzumab concurrent with chemotherapy and radiotherapy reached a median OS of 12.2 months (95% CI, 6.9–17.5) and 12- and 24-month survival rates of 51.0% and 17.0%, respectively. Median PFS was 7.8 months (95% CI, 6.2–9.5), and 12- and 24-month PFS rates were 39.3% and 11.2%, respectively. A favorable evolution of the general state of health ( p = 0.03 ) was obtained from the beginning of treatment until month 12, with a significant reduction in the appearance of nausea ( p = 0.009 ), insomnia ( p = 0.04 ), constipation ( p = 0.04 ), eating difficulties ( p = 0.0006 ), and choking when swallowing ( p = 0.0001 ), but increased in dysphagia ( p = 0.02 ). Conclusions. The administration of nimotuzumab was safe in the real-world setting. New diagnosed patients that received nimotuzumab concurrent with chemotherapy and radiotherapy reached a higher overall and progression-free survival and better quality of life than the rest of the patients. Trial registration is RPCEC00000215 (Cuban Registry of Clinical Trials; https://registroclinico.sld.cu/en/home). It is registered prospectively on June 30, 2016.