Purpose: This study aimed to evaluate the effectiveness of an interactive virtual reality (VR) play intervention including instructional play and emotional catharsis play sessions in reducing children's pain and fear during intravenous placement. Methods: A randomized controlled trial with parallel groups was conducted. The sample consisted of 134 hospitalized children aged 6–12 years (intervention group: n = 69; comparison group: n = 65). The intervention involved one immersive intravenous scene in VR before the actual intravenous placement and one emotional catharsis VR play after injection. The comparison group received an educational photo book about intravenous placement before receiving intravenous placement. The children and their caregivers rated their pain and fear by using the Wong–Baker FACES Pain Rating Scale and the Children's Fear Scale. The time required for successful intravenous insertion was also compared between the two groups. Results: Children's pain (p = .028) and fear scores (p = .004) were significantly lower in the intervention group than in the comparison group. Their caregivers' pain and fear scores (both p < .001) were significantly lower in the intervention group. The time required for successful intravenous insertion did not differ significantly between the intervention and comparison groups. Conclusions: The interactive play intervention with VR effectively reduced children's levels of pain and fear during the intravenous placement procedure. The results of this study can serve as a reference for the implementation of a feasible, child-friendly care practice for clinical intravenous placement in school-aged children.