Background: De-novo donor and non-donor specific antibodies could be detrimental to the kidney allograft. Kidney transplantation has being performed in Mongolia since 2006. However there is currently no published data available on post-transplant de-novo antibodies and long-term graft survival. Our aim was to determine immunosuppressive drug through level, its combination, de-novo HLA antibodies and its influence on graft survival in different immunosuppressive protocols. Methods: We analyzed data from 56 adult first kidney transplant recipients at our hospital from August 2006 to May 2013. We determined the level of tacrolimus, cyclosporine A, and the presence of pre and post-transplant anti-HLA antibodies. Results: Post-transplant follow up period was 1-8 years. Mean recipient age on transplantation was 33.9±9.1 years. Male 45 (80.4%). Cadaver donor kidney was 5 (8.9%). Mean donor age on transplantation was 39.98±11.13 years. Rejection occurrence was 12(21.4%). Tacrolimus and cyclosporine A through levels were 3-12.8ng/ml and 65- 324ng/ml respectively. Anti-HLA class I antibodies were detected in 17.9% of pretransplantation (n=10) and in 23.2% of post-transplantation (n=13) cases respectively (p=0.607). On the other hand, anti-HLA class II antibodies were detected in 5.4% of pretransplantation (n=3) and in 33.9% of post-transplantation (n=19) cases (p=0,001). We determined anti-HLA class II antibody specificity. Anti-DQ, DR, DP antibodies were 25% ( n=14), 14.3% ( n=8) and 7.1% ( n=4) respectively on all 56 cases. Two (3.6%) patients’ samples were positive on three loci of HLA class II. Six patient samples (10.7%) were positive on two loci. Nine (64.3%) of anti-DQ positive patients have rejected their grafts and begun hemodialysis treatment. All 9 graft rejected recipients were anti-HLA DQ positive and had taken cyclosporine mono-therapy for the first year after transplantation. Conclusion The presence of de-novo anti-HLA class II antibodies, especially de-novo anti-DQ were significantly increased on cyclosporine mono-therapy group following transplantation and negatively affected kidney graft survival. The blood through level of cyclosporine was very variable. The graft survival was better in standard triple regimen. Therefore, it is essential to monitor immunosuppressive drug combinations with drug blood level and anti-DSA antibodies as well as to manage antibody removal therapies such as therapeutic plasma exchange, intravenous immunoglobulin and Rituximab therapy on time. HLA –DQ-DP antigen determination is important for the kidney transplantation.