Whether insomnia, a known correlate of depression, predicts depression longitudinally warrants elucidation. The authors examined 555 Wisconsin Sleep Cohort Study participants aged 33-71 years without baseline depression or antidepressant use who completed baseline and follow-up overnight polysomnography and had complete questionnaire-based data on insomnia and depression for 1998-2006. Using Poisson regression, they estimated relative risks for depression (Zung scale score > or =50) at 4-year (average) follow-up according to baseline insomnia symptoms and polysomnographic markers. Twenty-six participants (4.7%) developed depression by follow-up. Having 3-4 insomnia symptoms versus none predicted depression risk (age-, sex-, and comorbidity-adjusted relative risk (RR) = 3.2, 95% confidence interval: 1.1, 9.6). After multiple adjustments, frequent difficulty falling asleep (RR = 5.3, 95% confidence interval: 1.1, 27.9) and polysomnographically assessed (upper or lower quartiles) sleep latency, continuity, and duration (RRs = 2.2-4.7; P's < or = 0.05) predicted depression. Graded trends (P-trend < or = 0.05) were observed with increasing number of symptoms, difficulty falling asleep, and difficulty returning to sleep. Given the small number of events using Zung > or =50 (depression cutpoint), a limitation that may bias multivariable estimates, continuous depression scores were analyzed; mean values were largely consistent with dichotomous findings. Insomnia symptoms or markers increased depression risk 2.2- to 5.3-fold. These results support prior findings based on self-reported insomnia and may extend similar conclusions to objective markers. Heightened recognition and treatment of insomnia may prevent subsequent depression.