OBJECTIVE: To identify published studies assessing tuberculosis recurrence after successful treatment with standard short course regimens for six months to determine the strength and sufficiency of evidence to support current guidelines. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Cochrane clinical trials register, specialist tuberculosis journals, and reference lists. Only English language publications were eligible. REVIEW METHODS: Studies were included irrespective of methodology or quality. Abstracted information included inclusion and exclusion criteria for participants, duration of follow-up, and definitions of treatment success and disease recurrence. The primary outcome was the proportion of successfully treated patients recorded with recurrent tuberculosis during the follow-up period. RESULTS: 17 study arms from 16 studies met the inclusion criteria; 10 were controlled clinical trials and six were either studies done under programmatic conditions or observational studies from functioning tuberculosis programmes. Although several clinical trials supported the use of daily treatment regimens, studies reporting tuberculosis recurrence after intermittent regimens were limited. Few studies carried out under routine programmatic conditions reported disease recurrence. Overall there was wide variation in recurrence after successful treatment, ranging from 0% to 14%. Considerable heterogeneity across studies precluded the systematic assessment of factors contributing to tuberculosis recurrence. CONCLUSIONS: Despite DOTS (directly observed treatment, short course) being implemented for more than 10 years and millions of patients treated for tuberculosis, few studies have assessed the ability of standard DOTS regimens to result in lasting cure for patients treated under routine programmatic conditions.