Aim: Postoperative lymphorrhea is a major complication of axillary lymphadenectomy. The aim of our study was to evaluate the impact of type I collagen in postoperative lymphorrhea in mastectomy patients. Methods: Eighty patients that underwent modified radical mastectomy for breast cancer were randomized in two groups. In group A (collagen group, n = 42) collagen type I (Cellerate RX powder) was applied in the axillary cavity after lymphadenectomy while in group B (control group, n = 38) lymphadenectomy was performed in the standard fashion without the use of a sealant. Suction drains remained in place until the daily amount of lymphatic drainage fell under 30 ml. The total amount and the duration of drainage, as well as the morbidity and severity of arm pain were compared in the two groups. Results: There was a non significant trend towards lower overall drainage in the collagen group. The duration of drainage and postoperative pain were similar in the two groups, as was morbidity. Subgroup analysis of patients according to the number of lymph nodes excised, revealed significantly less lymphorrhea in terms of volume and duration in patients who had more than ten lymph nodes excised. Conclusion: Collagen type I (Cellerate RX powder) appears to attenuate postoperative lymphorrhea in patients undergoing axillary lymphadenectomy especially when > 10 lymph nodes are removed.