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Microsurgeons may choose to avoid caffeine to prevent potentially deleterious caffeine tremor, although an adverse effect on surgical skill has never been shown. This double-blind placebo-controlled crossover study investigated the effect of moderate caffeine intake on microsurgical ability among microsurgical training course attendees. Subjects were randomized to receive either morning placebo and afternoon caffeine, or the reverse, thereby acting as their own controls. Performance in end-to-end vessel anastomosis was graded by a single observer during both sessions using a global rating scale. Subjects consuming caffeine in the morning demonstrated significantly improved scores from morning to afternoon, whereas subjects consuming caffeine in the afternoon showed no such improvement. These results are consistent with an adverse effect of caffeine on microsurgical skill combined with a learning curve among the study population of novice microsurgeons, and support the view that caffeine has a detrimental effect on microsurgical ability among this study group.