Complete remission can be achieved in 60–80% of adults with diffuse aggressive non-Hodgkin's lymphoma. However, 20–40% of them will subsequently relapse. Nevertheless, formal follow-up guidelines for recurrence detection have never been advocated. We analyzed the pattern of relapse in 30 patients with intermediate- and high-grade non-Hodgkin's lymphoma and the value of intensive protocol for relapse detection. This protocol includes frequent follow-up visits, complete blood count, and serum LDH tests along with annual chest, abdominal, and pelvic CT scans. The median duration of complete remission was 12 months. Twenty-five relapses (83%) were suspected after an interim history and /or physical examination, whereas only 5 relapses (17%) were detected by routine radiographic or laboratory follow-up studies. The majority of relapses (19/30) were detected in sites that included the sites of prior disease. For the first 12 months of complete remission, the estimated cumulative save in charge for a follow-up strategy, based on regular visits in the hematology clinic and performing laboratory and radiologic studies as clinically indicated, is 44% of the cost of a routine intensive evaluation. A reliable and cost-effective follow-up method for non-Hodgkin's lymphoma patients in complete remission should include frequent history and physical examination. Complementary studies should be performed according to clinical indications. Am. J. Hematol. 69:41–44, 2002. © 2002 Wiley-Liss, Inc.