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Background: Paired-associative stimulation (PAS) represents a neurophysiologic paradigm that involves peripheral nerve stimulation (PNS) of the median nerve, followed by the transcranial magnetic stimulation (TMS) of the contralateral motor cortex. PAS has been shown to result in long-term potentiation-like activity (PAS-LTP) if PNS precedes TMS by 25 milliseconds (PAS-25). PAS-LTP has also been shown to relate to simple motor performance. However, to date, no studies have directly investigated whether the induction of PAS-LTP is associated with enhanced motor learning., Objective: The objective of this study was to assess the short- and long-term effect of PAS-25 on motor learning., Methods: This was a randomized controlled pilot study in which the control condition was PAS-10, whereby PNS precedes TMS by 10 milliseconds. Motor learning was assessed using the rotary pursuit task at baseline prior to PAS-25 or PAS-10 and 45 minutes and 1 week post-PAS., Results: As expected PAS-25 but not PAS-10 was associated with PAS-LTP as indexed by a significant potentiation of the motor evoked potential. Also, PAS-25 resulted in enhanced motor learning at 1 week post-PAS (F (2, 44) = 3.441, P = .041)., Conclusions: This is the first PAS study showing long-term behavioral effect and suggests, albeit indirectly, that PAS-25 can trigger slowly manifesting cellular and structural changes that result in long-term improvement in motor performance. Larger studies with neurophysiologic or neuroimaging outcomes are needed to confirm such preliminary findings., (Copyright © 2011 Elsevier Inc. All rights reserved.)