Epidermal growth factor receptor inhibitors (EGFRIs) can potentially cause a debilitating rash despite use of reactive-based treatment. Prophylactic rash management is a controversial rash-mitigating approach. The impact of a prophylactic rash treatment protocol for EGFRIs at a community hospital was evaluated. This was a retrospective, institutional review board-approved examination of patient data for those patients who received EGFRIs from August 1, 2012, through May 31, 2015. Patients were grouped according to treatment with EGFRIs prior to standardized prophylactic rash management protocol (August 1, 2012, through July 31, 2014) and treatment after protocol implementation (September 1, 2014, through May 31, 2015). The outcomes measured included incidence of rash within the 6-week treatment period and occurrence of EGFRI dose reductions and/or delays. Of the 44 patients eligible for the analysis, 29 were evaluated in the reactive treatment group and 15 in the rash prophylaxis group. The incidence of rash over the 6-week EGFRI treatment period was 76% and 47% for the reactive treatment and rash prophylaxis groups, respectively (p = .09). There was a lower incidence of EGFRI dose delays and modifications in the rash prophylaxis group compared to the reactive treatment group: 26.7% and 6.7% compared to 41.4% and 20.7%, respectively. There was an overall decrease in rash incidence seen in patients who received prophylactic intervention; however, due to the failure to meet statistical significance and power, it is not possible to determine if rash prophylaxis decreases EGFRI rash incidence.