In the past 10 years there has been an emphasis on the risk of upper gastrointestinal bleeding in patients taking SSRI antidepressants. Few studies have concurrently examined the possible risk of traditional antidepressants or atypical antidepressants such as venlafaxine, classified as a serotonin-norepinephrine reuptake inhibitor. In order to promote debate about possible risk of upper gastrointestinal bleeding in elderly patients taking antidepressants different from SSRIs, we report a case of venlafaxine-induced upper gastrointestinal bleeding in a 84 years old woman. Discussion about safer drugs and protective factors is provided.