Since the introduction of calcineurin inhibitors, there has been a significant improvement in the results of solid organ transplantation including graft and patient survival. However, high cost, chronic nephrotoxicity and other side effects stand as major challenges for long-term use of these drugs. The long-term safety and financial benefits of the combination ketoconazole-cyclosporine previously studied. However, data about the effect of ketoconazole addition to tacrolimus-treated patients are scarce. Therefore, this study was conducted to evaluate safety and financial impact of that combination. The subject of this work included 70 live-donor kidney transplant recipients receiving tacrolimus. Their age ranged from 16-45 years. Among them, 54 were males and 16 were females. All of them were 6 months or more post-transplantation. Patients were randomly divided into two equal groups. Group I patients initially received ketoconazole 100 mg/day in addition to their usual treatment while group II patients were considered as control. Patients were followed up for 2years. Concomitant ketoconazole-tacrolimus resulted in marked reduction of tacrolimus dose (by 59.87 %) and cost (by 56.9%). It also resulted in significant improvement in graft function (Serum creatinine in Keto 1.58 mg/dl ± 0.39 Versus 1.79 mg/dl ± 0.76 in control group) group and fungal skin infection beside decrease of gastrointestinal episodes and hospitalization. We conclude that ketoconazole-tacrolimus combination in kidney transplant recipients is safe, has outstanding impact on treatment costs and improves patient and graft outcome over 2 years .