We have systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of isoniazid preventive therapy (IPT) in renal transplant recipients. Electronic databases Medline, Embase, and Cochrane Library (up to April 2010) were searched to identify relevant publications. Two reviewers independently applied the study selection criteria, examined study quality and extracted data. Data were expressed as risk ratios with 95% confidence intervals (CIs), and all statistical analyses were performed using Review Manager 5.0. Three RCTs met our selection criteria, including 657 patients (300 versus 357). Differences between IPT and control for post-transplant tuberculosis (TB) (risk ratios = 0.38; 95% CI 0.12–1.16; P = 0.09), extrapulmonary TB (risk ratios = 0.28; 95% CI 0.02–4.85; P = 0.38), TB-related deaths (risk ratios = 6.32; 95% CI 0.27–150.32; P = 0.25), and hepatitis (risk ratios = 1.05; 95% CI 0.72–1.55; P = 0.78) were not statistically significant. None of the three RCTs reported serious adverse effects related to IPT. On current evidence, IPT cannot be recommended as routine practice for the prevention of postrenal transplant TB, even in countries where TB is endemic.