Purpose <p>Paclitaxel and albumin-bound paclitaxel are important anticancer drugs for the treatment of non-small cell lung, pancreatic, gastric, and gynecological cancers; however, they cause peripheral neuropathy as an adverse reaction. Therefore, prophylaxis and treatment for peripheral neuropathy are needed, since there are no sufficient evidence-based strategies to prevent it. Our previous animal research and adverse effect database analysis studies have identified the potential of α1 antagonists to attenuate paclitaxel-induced peripheral neuropathy (PIPN). The purpose of the present study was to investigate the prophylactic potential of α1 antagonists for PIPN in patients with cancer.</p> Methods <p>Data were collected from the medical records of 673 male patients aged 18&#xa0;years and older who started treatment with paclitaxel- or albumin-bound paclitaxel-containing regimens at Kyushu University Hospital between January 1, 2013, and December 31, 2019. The two primary outcome measures were PIPN occurrence and paclitaxel discontinuation due to PIPN. Kaplan–Meier curves were generated for cumulative doses and evaluated using the log-rank test.</p> Results <p>The percentage of patients in whom PIPN occurred (any grade) during the entire study period was 37.4% and 20.0% in without and with α1-receptor antagonist groups, respectively (<i>P</i> = 0.0101, <i>χ</i>² test). The incidence of PIPN (any grade) was significantly lower in the α1 antagonists combination group (<i>N</i> = 55) than in the no α1-receptor antagonists group (<i>N</i> = 618) (<i>P</i> = 0.0425, log-rank test). However, there were no significant differences between the two groups in the discontinuation of paclitaxel due to PIPN (<i>P</i> = 0.9654).</p> Conclusions <p>The present retrospective cohort study may suggest that concomitant use of α1-receptor antagonists may moderate the development of PIPN.</p>