Objective: To establish whether using alternating arms for peripheral intravenous epirubicin administration affects the severity or duration of epirubicin‐induced phlebitis. Methods: An observational study of women with breast cancer (n = 237) in a UK Cancer Centre. Data were analysed after receiving three treatment cycles according to the arm used for epirubicin administration: same, alternating or mixed arm (two consecutive cycles in one arm and one in the alternate arm). Phlebitis severity was graded by clinical staff after each treatment; participants also self‐reported symptoms during treatment and for up to 6 months after. Results: The alternating arm group experienced significantly less severe symptoms than the other arm use groups, 6% (4 of 64) compared with 34% (p < 0.001, odds ratio: 0.13 (95% CI: 0.043–0.38) alternating arm compared with same arm group). The alternating arm group reported less pain (p = 0.013), lower overall impact (p = 0.009), lower effect on function (p = 0.032) and shorter duration of symptoms (p = 0.001) than the other arm use groups. Conclusion: Using alternating arms for peripheral administration of epirubicin significantly reduces the severity and duration of chemical phlebitis and is recommended to improve patient experience and reduce the need for central venous access devices.