Background: Laparoscopic surgery has been shown to provide important advantages in comparison with open procedures in the treatment of several malignant diseases, such as less perioperative blood loss and faster patient recovery. It also maintains similar results with regard to tumor resection margins and oncological long-term survival. In gastric cancer the role of laparoscopic surgery remains unclear. Methods/Design: The Surgical Techniques, Open versus Minimally invasive gastrectomy After CHemotherapy (STOMACH) study is a randomized, clinical multicenter trial. All adult patients with primary carcinoma of the stomach, in which the tumor is considered surgically resectable (T1-3, N0-1, M0) after neo-adjuvant chemotherapy, are eligible for inclusion and randomization. The primary endpoint is quality of oncological resection, measured by radicality of surgery and number of retrieved lymph nodes. The pathologist is blinded towards patient allocation. Secondary outcomes include patient-reported outcomes measures (PROMs) regarding quality of life, postoperative complications and cost-effectiveness. Based on a non-inferiority model for lymph node yield, with an average lymph node yield of 20, a non-inferiority margin of -4 and a 90% power to detect non-inferiority, a total of 168 patients are to be included. Discussion: The STOMACH trial is a prospective, multicenter, parallel randomized study to define the optimal surgical strategy in patients with proximal or central gastric cancer after neo-adjuvant therapy: the conventional 'open' approach or minimally invasive total gastrectomy.