Electrocautery has been postulated as a factor in the risk of seroma formation after mastectomy. Eighty consecutive mastectomies in 74 patients were randomly assigned to dissection of the mastectomy flaps with either scalpel (n = 38) or electrocautery (n = 42). Total volume of fluid output through drains and aspirated from seromas was recorded. Other factors investigated included the type of drain utilized, estimated blood loss, and complications. Seromas developed in 16 wounds in the electrocautery group compared with 5 in the scalpel group (38% and 13%, respectively; P = 0.01). Other factors with an independent risk for seroma included use of Jackson-Pratt drains compared with Blake drains (P = 0.006), and lower estimated blood loss (P = 0.006). No differences in characteristics of patients or in other complications were noted. Use of electrocautery to create skin flaps in mastectomy reduced blood loss but increased the rate of seroma formation.