Background: Modified radical mastectomy (MRM), as a surgical treatment in breast cancer patients, may lead to important complications with significant morbidities including seroma formation. Objective: This study aimed to determine the effect of wound irrigation with topical phenytoin on postoperative seroma formation after modified radical mastectomy. Patients and methods: This is a double-blinded randomized clinical trial study, which was carried out in Zagazig University Hospital during a period of 6 months. It included 60 patients who were candidates for modified radical mastectomy (MRM). All patients were subjected to demographic data taking, clinical and chemical examination, clinical evaluation, radiological evaluation, Lab. Investigations. Results: Average daily breast drainage (in milliliters) of drains according to their location and day of evaluation: Group A (Phenytoin) in day 5 drained a mean of 24.62 with SD of 32.79, in day 7 mean of drainage was 28.89 and SD was 18.33, in days 8 to 10 mean of drainage was 32 and SD was 10.95, and in days 11 to 13 mean of drainage was 15 and SD was 7.07. Group B (Control): day 5 group drained a mean of 35.88 with SD of 12.93, in day 7 mean of drainage was 28.18 and SD was 12.68, in days 8 to 10 mean of drainage was 21.43 and SD was 11.07, in days 11 to 13 only one patient in control group had breast drain after 11^th postoperative day drainage was 50 and in days 14 to 16 drainage was 20. Conclusion: Topical irrigation of the surgery site with phenytoin was effective in reducing axillary surgical wound drainage.