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Aims To compare the acute effects of alcohol on set-shifting task performance (relative to sober baseline performance) during ascending and descending limb breath alcohol concentration (BrAC), as well as possible moderation of these effects by baseline individual differences. Design Shifting performance was tested during an initial baseline and a subsequent drinking session, during which participants were assigned randomly to one of three beverage conditions (alcohol, placebo or control) and one of two BrAC limb conditions [ascending and descending (A/D) or descending-only (D-only)]. Setting A human experimental laboratory on the University of Missouri campus in Columbia, MO, USA. Participants A total of 222 moderate-drinking adults (ages 21-30 years) recruited from Columbia, MO and tested between 2010 and 2013. Measurements The outcome measure was performance on set-shifting tasks under the different beverage and limb conditions. Shifting performance assessed at baseline was a key moderator. Findings Although performance improved across sessions, this improvement was reduced in the alcohol compared with no-alcohol groups (post-drink latent mean comparison across groups, all Ps ≤ 0.05), and this effect was more pronounced in individuals with lower pre-drink performance (comparison of pre- to post-drink path coefficients across groups, all Ps ≤ 0.05). In the alcohol group, performance was better on descending compared with ascending limb ( P ≤ 0.001), but descending limb performance did not differ across the A/D and D-only groups. Conclusions Practising tasks before drinking moderates the acute effects of alcohol on the ability to switch between tasks. Greater impairment in shifting ability on descending compared with ascending breath alcohol concentration is not related to task practice. [ABSTRACT FROM AUTHOR]