OBJECTIVE The stomach is the most common site of origin for extranodal lymphomas. While resection has played a major part in the management of such patients in the past, in recent years there has been a change towards organ-conserving therapies. However, the risk of perforation and bleeding in patients undergoing organ-conserving therapy has been used as an argument against primary application of chemotherapy. In this article, we present our experience with the prophylactic use of oral pantoprazole. METHODS All patients undergoing chemotherapy for gastric lymphoma at our institution were prophylactically given oral pantoprazole (2x40 mg) for the duration of chemotherapy. Compliance with intake of the proton-pump inhibitor (PPI) was assessed at every visit for application of chemotherapy and at routine blood counts taken 10-14 days after each cycle of treatment by direct questioning of the patient. RESULTS A total of 82 patients (median age 69 years, range 33-93) received chemotherapy for gastric lymphoma: 51 had diffuse large B-cell lymphoma (DLBCL), 24 had mucosa-associated lymphoid tissue (MALT) lymphoma and 7 had DLBCL+MALT lymphoma. Compliance with intake of the PPI was excellent, as only two patients reported irregular intake and only one patient refused regular medication with pantoprazople. All patients responded to chemotherapy, with 74 (90%) achieving complete remission and 8 (10%) partial remission. After a median follow-up time of 50 months (range: 9-84 months) only one of these 82 patients (1.22%), the patient who discontinued intake of pantoprazole, died from gastric perforation, while none of the other patients had gastrointestinal bleeding or perforation. CONCLUSIONS Judging from these data, continuous PPI intake is feasible and has a high rate of compliance. In the absence of randomized trials, routine application of oral pantoprazole in patients given chemotherapy for gastric lymphoma, especially DLBCL, appears to be a reasonable approach.