Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). In this study we investigated if one-hour infusions of VCR instead of push-injections reduces VIPN in pediatric oncology patients. We conducted a multicenter randomized controlled trial in which participants received all VCR administrations through push injections or one-hour infusions. VIPN was measured at baseline and 1–5 times during treatment using Common Terminology Criteria of Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score. Moreover, data on co-medication, such as azole antifungals, were collected. Overall, results showed no effect of administration duration on total CTCAE score or ped-mTNS score. However, total CTCAE score was significantly lower in patients receiving one-hour infusions concurrently treated with azole antifungal therapy (β = -1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VCR push injections in pediatric oncology patients. However, one-hour infusions lead to less severe VIPN compared to push-injections when azole therapy is administered concurrently with VCR. These results indicate that in children treated with VCR and requiring concurrent azole therapy, one-hour infusions might be beneficial over push injections, although larger trials are needed to confirm this association.