OBJECTIVE: To compare therapeutic efficacy and safety of different chemotherapy regimens in the treatment of small cell esophageal cancer. METHODS: In retrospective analysis, 58 patients with small cell esophageal cancer were divided into group A(18 cases),B(26 cases) and C(14 cases) according to chemotherapy regimens. Group A was given Cisplatin injection 75 mg/m2 intravenously, d1-3+Paclitaxel injection 175 mg/m2,d1-3. Group B was given Cisplatin injection 30 mg/m2 intravenously,d1-3+Etoposide injection 100 mg/m2,d1-3. Group C was given Vinorelbine tartrate injection 25 mg/m2 intravenously, d1-3+Gemcitabine hydrochloride for injection 1 000 mg/m2,d1-3. A treatment course of 3 groups lasted for 21 d, and they all received 2 cycles of treatment. Clinical efficacies, 1, 2, 3-year survival rate and the incidence of Ⅲ-Ⅳ degree toxic reaction (cough, fever, expectoration, shortness of breath, fatigue, chest pain, bone marrow suppression, gastrointestinal reactions) were compared among 3 groups. RESULTS: Total response rate and 1, 2, 3-year survival rate were in descending order: group C>group B>group A; the incidence of Ⅲ-Ⅳ degree cough, fever, expectoration, shortness of breath, fatigue, chest pain were in ascending order: group C<group B<group A, with statistical significance (P<0.05). There was no statistical significance in the incidence of Ⅲ-Ⅳ degree myelosuppression and digestive tract reaction among 3 groups (P>0.05). CONCLUSIONS: Therapeutic efficacy and 1,2,3-year survival rate of vinorelbine combined with gemcitabine are significantly higher than those of cisplatin combined with paclitaxel or etoposide with better safety.