Rationale: An effective new TB vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global healthcare. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open label, Phase I trial of MVA85A was performed in 12 individuals with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. ClinicalTrials.gov ID NCT00456183. Patients were assessed clinically and had bloods drawn for immunological analysis over a 52 week period following vaccination with MVA85A. Thoracic CT scans were performed at baseline and at 10 weeks following vaccination. Safety of MVA85A was assessed by clinical, radiological and inflammatory markers. The immunogenicity of MVA85A was assessed by IFN and IL-2 ELISpot assays and FACS. Measurements and main results: MVA85A was safe in individuals with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic CT scans following vaccination. MVA85A induced a strong antigen specific IFN- and IL-2 response that was durable for 52 weeks. The magnitude of IFN- response was comparable to previous trials of MVA85A in BCG vaccinated individuals. Antigen-85A specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers following vaccination. Conclusion: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB endemic areas. Clinical trials registry information: ID#NCT00456183 registered at http://www.clinicaltrials.gov