BACKGROUND: Tuberculosis (TB) remains a leading cause of death in endemic countries and is 20 to 70 times more common in renal transplant recipients, where it contributes to both increased morbidity and mortality. This review will focus on the epidemiology of TB in renal transplant recipients and critically appraise the published literature on isoniazid prophylaxis in renal transplantation. METHODS: A literature search for randomized and nonrandomized studies investigating the use of isoniazid prophylaxis in renal transplant recipients was conducted using Ovid MEDLINE, the Cochrane Library, the Transplant Library, and EMBASE. Relative risks (RRs) with 95% confidence intervals (CIs) are reported. Meta-analysis of the randomized controlled trials (RCTs) was performed with a fixed-effects model. RESULTS: Eleven relevant studies were identified; six nonrandomized and five RCTs. The nonrandomized studies indicate a reduced risk of TB with isoniazid prophylaxis. The RCTs demonstrated conflicting results, with two studies finding a reduction in TB with prophylaxis and two studies finding no difference. Meta-analysis of the 709 patients from the four RCTs demonstrated a reduced risk of TB with isoniazid prophylaxis (RR, 0.31; 95% CI, 0.19-0.51). No significant difference was found in the incidence of hepatitis (RR, 1.22; 95% CI, 0.91-1.65). CONCLUSION: Both randomized and nonrandomized studies support the value of isoniazid as TB prophylaxis in renal transplant recipients at risk of active infection. Clinicians should consider prophylaxis in renal transplant recipients in endemic areas or in recipients in nonendemic countries who are at risk. However, the evidence for the benefit of isoniazid prophylaxis in renal transplantation is not robust and there is still a need for a large multicenter trial of isoniazid prophylaxis in kidney transplantation in an endemic area.