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Targeted memory reactivation represents an established technique for promoting sleep-dependent memory consolidation in laboratory studies. This investigation aimed to test the potentiality of a wearable electroencephalography-based closed-loop targeted memory reactivation system to boost vocabulary learning in home settings. In the evening, 24 adults (23.58 years ± 3.36 years, 19 females) were asked to learn the Italian translation of 40 pseudowords (test session). Subsequently, participants slept at their home wearing an electroencephalography headband (Dreem 2), and half of the pseudowords were acoustically re-presented (cued) following the real-time detection of slow waves. After the awakening, memory recall of the Italian translations was retested. The stimulation effect was evaluated by comparing the test-retest variations in memory accuracy between cued and uncued pseudowords. Moreover, we assessed the event-related potentials and spectral perturbations induced by the cued stimuli during sleep, comparing the electrophysiological correlates of correctly translated pseudowords with incorrectly translated ones at the retest session. Closed-loop targeted memory reactivation increased the translation accuracy for cued pseudowords (+8.6%), while no significant test-retest variation for uncued items was observed (-4.6%). Time-frequency analysis indicated a spectral power increase in the spindle frequency band coinciding with the second positive peak of the sound-elicited slow wave as the correlate of successful morning recall. This study extended the targeted memory reactivation effectiveness in enhancing vocabulary learning to an ecological home environment, providing further support to the role of spindle activity in the targeted memory reactivation effect. A wearable closed-loop targeted memory reactivation system could represent a memory-enhancement tool in real-world settings by promoting the hallmark sleep electroencephalographic rhythms of memory consolidation., (© 2025 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)