Recent literature suggests that a positive crossmatch adversely impacts outcomes in simultaneous liver-kidney transplant (SLKT). The aim of this study was to evaluate outcomes of SLKT with a positive flow crossmatch (+FCXM) at our center. We retrospectively analyzed all of the SLKTs between January 1, 2000, and September 30, 2010. A total of 2793 kidney transplants and 892 liver transplants were performed in this time period, of which, 31 were SLKT (3%). Seven of the 31 (22%) SLKTs had a +FCXM. There were 3 major adverse events: 1 patient mortality at 9 months with liver failure; 1 allograft nephrectomy for primary nonfunction secondary to hyper-acute rejection; and, 1 recurrent liver allograft rejection with eventual graft loss and death at 26 months post-transplant. The median follow-up time was 34 months. The 3-year overall SLKT patient survival in the negative FCXM (-FCXM) patients was 85% compared with 71% in the +FCXM group. The rates of acute liver and kidney rejection were 6% and 10%, respectively, in the -FCXM group compared to 14% and 28%, respectively, in the +FCXM group. A very strongly +FCXM with a mean channel shift above 4 times the positive cut-off and the presence of multiple strong donor-specific antibodies (DSA) with mean fluorescence intensity (MFI) above 10,000 were associated with poorer outcome. In conclusion, in patients with very strongly +FCXM with high MFI DSA, proceeding with the transplantation leads to poor outcomes.