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To determine whether greater frequency and severity of hot flashes are independently associated with insomnia symptoms and objective measures of disrupted sleep among healthy postmenopausal women with hot flashes.A baseline cross-sectional analysis of a multicenter, randomized trial in 217 healthy postmenopausal women aged 40 to 60 years with hot flashes was conducted. Hot flash frequency and severity were recorded in a daily diary; frequency of moderate to severe hot flashes was the primary measure. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI). Hot flash frequency and severity and objective parameters of sleep-wake patterns (using a wrist actigraph) were concurrently measured over an average of seven consecutive 24-hour periods in a subcohort of 112 women.The mean age of participants was 54 years, and 80% were white; 33% had an ISI score greater than 14, consistent with at least moderate insomnia. In multivariable analysis, the mean ISI score showed a stepwise increase in magnitude with higher frequency of moderate to severe hot flashes (adjusted mean ISI score, 9.5, 11.4, 11.9, and 13.0 for quartiles 1-4, respectively; P for trend = 0.002). Higher frequency of moderate to severe hot flashes was also independently associated in a graded manner with greater nighttime wakefulness (P for trend = 0.028) and a higher number of long wake episodes (P for trend = 0.008) but was not related to sleep efficiency, total sleep time, or sleep latency.Among healthy postmenopausal women with hot flashes, frequency of moderate to severe hot flashes was independently associated in a graded manner with severity of insomnia symptoms and objective measures of nighttime wakefulness and sleep fragmentation.