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So far, several aspects of autobiographical memory (AM) have been found to be impaired in depression. Among others, depressed patients show the tendency to recall more negative than positive events (i.e., negative bias) and usually retrieve memories that lack of specificity and details (i.e., overgeneral memories). Based on this, we designed an AM task enhanced by the use of virtual reality (VR) to specifically train the recall of positive memories. Using a single-case, multiple baseline experimental design, we explored the effects of a brief intervention consisting of two sessions of this training in a sample of 18 individuals with moderate-to-moderately severe depressive symptoms. According to the results, changes occurred at the short term only. In particular, almost all participants reported a significant improvement in at least one outcome measure 0–3 days after the intervention. However, these clinical gains were not maintained in the mid-term (from day 4 to 10). The present findings do not support the efficacy of our VR-based AM recall treatment as a standalone intervention. Nevertheless, it might represent a suitable procedure to obtain immediate and/or short-term improvements. It might also serve as a valid component to be integrated in broader protocols for patients with moderate-to-moderately severe depressive symptoms., Highlights • There is increasing evidence supporting the association between depression and autobiographical memory impairments. • Addressing memory impairments represents a useful therapeutic tool for the treatment of depression. • Virtual reality could enhance the retrieve of positive events, thus making it a good candidate in memory interventions. • After the training, all participants reported a significant improvement in at least one outcome measure. • This training may be a suitable procedure to obtain immediate and/or brief-term improvements.