A wealth of studies supports the role of sleep in memory performance. Experimentally controlled studies indicate that prolonged wake after memory encoding is detrimental for memory outcome whereas sleep protects from wake-time interference and promotes memory consolidation. We examined how the natural distribution of wake and sleep between encoding and retrieval associated with overnight picture recognition accuracy among 161 adolescents following their typical sleep schedule with an in-home polysomnography. The memorized pictures varied in their level of arousal (calm to exciting) and valence (negative to positive). Suspecting genotypic influence on the sensitivity for sleep/wake dynamics, we also assessed if these associations were affected by known gene polymorphisms involved in neural plasticity and sleep homeostasis: brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-methyltransferase (COMT) Val158Met. In the whole sample, overnight recognition accuracy was associated with the levels of arousal and valence of the pictures, but not with sleep percentage (i.e. the percentage of time spent asleep between memory encoding and retrieval). While the allelic status of BDNF or COMT did not have any main effect on recognition accuracy, a significant moderation by BDNF Val66Met was found (p = .004): the subgroup homozygous for valine allele showed positive association between sleep percentage and recognition accuracy. This was underlain by detrimental influence of wake, rather than by any memory benefit of sleep. Our results complement the mounting evidence that the relation between sleep and memory performance is moderated by BDNF Val66Met. Further studies are needed to clarify the specific mechanisms.