Purpose: To retrospectively assess the efficacy and toxicity of single-agent methotrexate (MTX) regimen applied to patients treated in Anhui provincial hospital with low-risk gestational trophoblastic neoplasia (LR-GTN). Materials and Methods: Between 2005 and 2017, on the basis of International Federation of Gynecology and Obstetrics (FIGO 2000) criteria for staging and scoring system, 66 patients with LR-GTN were treated with single-agent MTX. The authors describe their clinical characteristics, resistance/remission/recurrence rates, and treatment toxicity. Results: All patients achieved remission and maintained disease-free status until the moment of analysis. The five-day MTX protocol can achieve a 63.6% remission rate. Resistance to this regimen was obviously related with age and higher pre-treatment hCG. Severe blood toxicity (grade 3 or 4) was shown in four (6.1%) of 66 cases, of which one (1.5%) case was grade 4. Conclusions: For patients diagnosed with LR-GTN, a five-day MTX regimen is an appropriate treatment associating a low rate of toxicity to a high rate of remission.