OBJECTIVES: Isoniazid is highly effective and widely used for TB prevention and treatment; however it must be used consistently for 6 to 9 months to treat latent TB, which is usually asymptomatic. The combination of long-term therapy and lack of symptoms results in high risk for non-adherence.  The cost of subsequent treatment for patients with isoniazid resistance is estimated at $1 million per reactivation case prevented. These data highlight the need for more information about adherence with isoniazid in patients with latent TB.  The specific aim of this study was to document adherence patterns in patients with latent TB and examine associations with patient characteristics. We also examined patient’s attitudes toward intentional nonadherence in relation to medical doubts, lack of social support, and medication side effects by using the Temptation to Skip Therapy (TEST) scale. METHODS: Questionnaires were completed at baseline by 211 isoniazid treated patients (aged 18-66) at the Rhode Island Tuberculosis Clinic. Adherence was subsequently measured at 6 and 9 months. The average score was computed for each TEST subscale and the association with each subscale and the Morisky Medication Adherence Scale (MAS) was examined.  RESULTS: Adherence to INH therapy was 45% (by MAS).  Latent TB patients scored highest on the Side Effect (Mean=1.62) and lowest on the TEST Medical Doubt subscale (Mean = 1.47). Non-Whites exhibited higher mean scores on the Medical Doubt subscale indicating uncertainty toward the need for therapy. Patients with higher scores on the Medical Doubt and Side Effect subscales had higher non-adherence levels. CONCLUSIONS: Latent TB patients exhibited low adherence with isoniazid therapy.  Fear of side effects and doubts about the need for medication were related to discontinuation of therapy. Better understanding of attitudes toward isoniazid therapy may be beneficial for improving adherence, and reducing costs associated with isoniazid treatment.