Background <p>Vinorelbine (VNR) is a key chemotherapeutic agent for treating non-small cell lung cancer (NSCLC). However, peripheral venous administration frequently induces phlebitis in 20–50% of patients. A previous study showed that applying a hot compress during VNR was effective in patients who had already developed symptoms. Therefore, this method was applied to all patients receiving VNR via peripheral venous administration at Hokkaido University Hospital. Herein, we aimed to evaluate the prophylactic efficacy of hot compresses for VNR-induced phlebitis in real-world settings.</p> Methods <p>Patients with NSCLC who received cisplatin (CDDP) + VNR (<i>n</i> = 92) were retrospectively evaluated. Patients were divided into a hot compress group, which included patients who received hot compresses during VNR administration, and a control group that did not receive hot compresses. The primary endpoint was the frequency of phlebitis during the first cycle between the groups.</p> Results <p>Hot compress significantly reduced the frequency of phlebitis during the first cycle (47.3% and 18.9% in the control and hot compress groups, respectively; <i>P</i> = 0.008) and on day 8 of the first cycle (38.2% and 10.8%; <i>P</i> = 0.004), with primary endpoint accomplishment. Furthermore, symptom reduction using hot compresses was confirmed among patients who received VNR on day 8 via a different arm from that administered on day 1 (31.6% vs. 3.0%, <i>P</i> = 0.002). Additionally, the onset of the first occurrence of VNR-induced phlebitis was significantly delayed (<i>P</i> = 0.008).</p> Conclusion <p>Hot compresses significantly reduced the frequency of VNR-induced phlebitis in patients with NSCLC receiving CDDP + VNR.</p>