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The present study aimed to investigate whether prematurity and perinatal stress exert long-term effects on the onset of panic disorder in later life. From 40,189 adults born in Germany between 1969 and 2002, a study cohort (n = 427) stratified by gestational age (GA) (extremely preterm: GA < 29 weeks; very preterm: GA 29–32 weeks; moderately preterm: GA 33–36 weeks; and full-term GA ≥ 37 weeks) was selected (age 28.5 ± 8.7 years). Multivariable logistic regression analyses were conducted to investigate associations between gestational age at birth and panic disorder adjusting for age, gender, socioeconomic status, and perinatal factors. The prevalence of panic disorder was roughly equal in moderate to very preterm and full-term birth groups at 1.9%–3.8%. However, this rate significantly increased to 14.3% in the extreme preterm category (GA <2 9: 14.3 %, p = 0.002). In multivariable analyses, female gender and GA were independently associated with panic disorder. Adjusting for age, gender and socioeconomic status, panic disorder was associated with lower GA at birth (OR = 1.12 per week (CI95%: 1.01–1.26, p = 0.037). Whereas adjustment for nutrition status or indicators of perinatal stress had no effect, correction for the length of postnatal ICU-stay eliminated the association between preterm birth and later panic disorder. Limitations include the small number of cases and the reliance on questionnaires to assess mental status. Prematurity likely increases the risk of panic disorder later in life, and the subsequent postnatal ICU-stay appears to be of critical importance. However, due to strong collinearity and other associated factors with preterm births, it remains unclear which is the primary determinant. [Display omitted] • Retrospective cohort study with prospective clinical and psychological assessment. • Extreme prematurity was associated with an increased prevalence of panic disorder later in life. • Persons born extremely preterm had a 4-fold higher prevalence of panic disorder. • Intensive care stay drives the association between prematurity and panic disorder onset. [ABSTRACT FROM AUTHOR]