Milacemide, both an MAO‐B inhibitor and a prodrug for glycine, has demonstrated cognitive enhancing effects in animal models, in cognitively intact young and elderly, and has been suggested as a potential treatment for senile dementia of the Alzheimer type (SDAT). This multicenter open‐label trial evaluated the safety and potential efficacy of long‐term milacemide treatment in 209 SDAT outpatients (50–87 years of age). Milacemide treatment was intiated at 400 mg/day and was titrated up to a maximum dose of 1,600 mg/day. Laboratory screening tests, adverse effects reports, the Clinical Global Impression Scale, and the Patient Global Improvement Rating Scale were collected to assess patients' physical and cognitive functioning. Only 8 of 209 patients completed 1 year of treatment and the remaining patients were withdrawn due to adverse effects (73), protocol violations (89), treatment failure (34), and failure to follow‐up (5). Liver function tests became elevated in 145 patients and required study withdrawal of 67 of these patients. There was no evidence of cognitive enhancement or reduction in disease progression. It does not appear that milacemide is a viable treatment for SDAT patients. © 1992 Wiley‐Liss, Inc.