BACKGROUND: There is an ongoing debate about whether clearance of Mycobacterium tuberculosis infection occurs and at what magnitude. Recent studies quantifying "uncertainty zones" of interferon-gamma release assays (IGRAs) provide a more stringent estimate of reversion. RESEARCH QUESTION: When accounting for uncertainty zones through stringent cutoffs, what are the trajectories of IGRAs results over 2 years of testing? STUDY DESIGN AND METHODS: Five cohorts from South Africa, China, Tanzania, and the United States tested with an IGRA 3 or more times were followed up for stringent conversion and reversion. The annual risk of IGRA reversion was assessed following an IGRA conversion and among those with baseline positivity. RESULTS: A total of 26,596 IGRA measurements were taken over 13,593 years of follow-up (Nparticipants = 7,683). Stringent reversion at year 2 following stringent conversion at year 1 varied between cohorts, occurring in 48% (43/90) for Wantai, 37% (22/59) for QuantiFERON, and 17% (2/12) for T-SPOT.TB, respectively. In the US cohorts, stringent reversion at year 1 following stringent conversion at 6 months was 58% (15 of 26) for QuantiFERON and 18% (12 of 60) for T-SPOT.TB. Stringent reversion at 1 year following baseline positivity occurred in 12% (47 of 404) for Wantai, 21% (10 of 48) for QuantiFERON, and 44% for T-SPOT.TB (45 of 102). In one cohort from China (N = 399; age range, 59 years [interquartile range, 48-67 years]), IGRA reversion was more common in younger participants (adjusted OR [aOR], 0.95; 95% CI, 0.93-0.97) and those without recent close TB exposure (aOR, 0.35 [95% CI, 0.11-1.03] in South Africa; aOR, 0.10 [95% CI, 0.01-0.61] in China). INTERPRETATION: These results suggest high annual rates of IGRA reversion, even with the use of uncertainty zones; reversion rates decreased over time from exposure and at older ages.