AIM: To explore the diagnosis and treatment of Mallory-Weiss syndrome (MWS). METHODS: A retrospective analysis was performed of 64 MWS patients treated at our hospital from January 2010 to March 2014. The causes, endoscopic findings, treatment and prognosis were evaluated according to a new type of clinical classification. RESULTS: The male to female ratio was 3.3:1 and the average age was 50.2 years old. Approximately 53.1% of MWS cases were caused by over-drinking or inappropriate diet occasionally, 37.5% caused by underlying gastric diseases such as peptic ulcer (26.6%), gastric cancer (6.3%) or Dieulafoy’s disease (4.7%), and 9.4% by endoscopic examination or treatment. 62.5% of MWS cases developed only one lesion of the cardia and/or lower esophagus and 29.7% developed two to three lesions. The lesions may occur in any location of the wall of the cardia and/or lower esophagus, with the right wall being a relatively common location (32.5%). According to a new type of clinical classification introduced here based on endoscopic examination, 17.2% of MWS cases were found to have active bleeding (type A) such as spouting, pulsating or oozing, 21.9% with a fresh blood clot (type B) and 32.8% with an old blood clot (type C). The rest (28.1%) was found to have linear ulcer or scar (type D). All type A patients were treated by endoscopic clipping, and some patients additionally underwent noradrenalin spraying. Some type B patients were treated by clipping or noradrenalin spraying. Only one type A patient died because of suspected underlying intestinal bleeding, and all other patients were cured. CONCLUSION: Underlying gastric diseases are important causes of MWS and easy to be ignored, especially Dieulafoy’s disease. Endoscopic clipping is the first choice of treatment for MWS, and the new type of clinical classification is useful for disease evaluation. © 2015 Baishideng Publishing Group Inc. All rights reserved.