This study aims to assess the effects of immersive Virtual Reality in people with cancer undergoing antiblastic therapy, on anxiety, fatigue and pain. This is a randomized controlled three-arm trial. Seventy-four cancer patients were recruited from a regional hospital in Italy, and randomly allocated into three groups: a Virtual Reality group (n=25), a narrative medicine group (n=25) and a standard care group (n=24). The primary outcome was anxiety. Secondary outcomes included fatigue and pain. The outcomes were evaluated immediately before and after the interventions. The findings showed that anxiety decreased more in the Virtual Reality group (Δpre-post = 6.24, 95% CI 2.578 to 9.902, p=.001, d = 0.63) than in the narrative medicine group, whereas it did not change for those in the standard care group. Fatigue decreased in the Virtual Reality group (Δpre-post = 0.576, 95% CI 0.246 to 0.907, p=.001, d = 0.23), while remaining stable in the narrative medicine group, and increasing in the standard care group. Average levels of pain did not change before and after the intervention [F(1,71) = 1.06, p=.307, ηp2 = .015]. Findings show that virtual reality is effective to reduce anxiety and fatigue in people with cancer undergoing antiblastic therapy. Virtual Reality can be recommended as an complementary intervention to manage anxiety and fatigue in people with cancer during antiblastic therapy. ClinicalTrials.gov NCT05629507.