To assess whether nocturnal symptoms of insomnia influence the prevalence of obstructive sleep apnea (OSA) in a clinical referral cohort. Insomnia was defined by the presence of 1 or more of the following complaints: difficulty initiating sleep, difficulty maintaining sleep, and/or early morning awakenings. OSA severity was based on an apnea-hypopnea index: ≥ 5.0 events/h (any OSA), ≥ 15.0 events/h (moderate/severe OSA), and ≥ 30 events/h (severe OSA). Multivariate logistic regression analysis was used to evaluate predictive factors for OSA diagnosis and severity. Overall, 12,021 outpatients referred for polysomnography were grouped into 2 cohorts: without insomnia (58.2%) and with insomnia (41.8%). Individuals without insomnia had a higher prevalence of OSA than those with insomnia (P < .001, for all OSA severity levels). The presence of insomnia was negatively associated with diagnosis of any OSA (adjusted odds ratio: 0.852; 95% confidence interval: 0.769-0.944), moderate/severe OSA (adjusted odds ratio: 0.819; 95% confidence interval: 0.751-0.892), and severe OSA (adjusted odds ratio: 0.816; 95% confidence interval: 0.746-0.892). Moreover, the number of nocturnal symptoms of insomnia was associated with a lower likelihood of OSA, even when adjusted for other confounders such as sex, age, body mass index, neck circumference, excessive daytime sleepiness, hypertension, and type 2 diabetes mellitus. In this present study that included a large sample of consecutive outpatients, there was an inverse relationship between the number of nocturnal symptoms of insomnia and OSA diagnosis. Duarte RLM, Magalhães-da-Silveira FJ, Gozal D. Influence of nocturnal insomnia symptoms on obstructive sleep apnea diagnosis in a clinical referral cohort. J Clin Sleep Med. 2022;18(5):1271-1278.