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The efficacy of decoction in extracting mycobactericidal compounds from Flourensia cernua (Hojas ́e) leaves and fractionationwith solvents having ascending polarity was compared with that of (i) ethanol extraction by still maceration, extraction witha Soxhlet device, shake-assisted maceration, or ultrasound-assisted maceration, followed by fractionation with n-hexane, ethylacetate, and n-butanol; (ii) sequential extraction with n-hexane, ethyl acetate, and n-butanol, by still maceration, using a Soxhletdevice, shake-assisted maceration, or ultrasound-assisted maceration. The in vitro mycobactericidal activity of each preparationwas measured against drug-sensitive (SMtb) and drug-resistant (RMtb) Mycobacterium tuberculosis strains. The results of whichwere expressed as absolute mycobactericidal activity (AMA). These data were normalized to the ΣAMA of the decoction fractionset. Although decoction was inactive, the anti-RMtb normalized ΣAMA (NAMA) of its fractions was comparable with theanti-RMtb NAMA of the still maceration extracts and significantly higher than the anti-SMtb and anti-RMtb NAMAs of everyother ethanol extract and serial extract and fraction. Hexane extracted, from decoction, material having 55.17% and 92.62% ofantituberculosis activity against SMtb and RMtb, respectively. Although the mycobactericidal activity of decoction is undetectable;its efficacy in extracting F. cernua active metabolites against M. tuberculosis is substantially greater than almost all pharmacognosticmethods.