Abstract Background The combination of Pentoxifylline (Trental) and vitamin E has been reported to reverse significant consequences of radiation post-mastectomy with immediate reconstruction, such as severe capsular contracture or loss of implants. We questioned whether prophylactic use could prevent these consequences. Methods 30 women with implants or tissue expanders post-mastectomy that underwent adjuvant radiation were treated with Trental and vitamin E for 180 days. All subjects then entered a twelve-month observational phase. Results Of the 26 evaluable subjects, three subjects required implant revisions. One due to malposition of the non-radiated breast and two were due to contracture (7.7%). There were no implant losses. Conclusion The combination of Trental and vitamin E can prevent severe contracture and implant losses allowing for immediate reconstruction with implant or tissue expander even if radiation is planned post mastectomy.