This study aimed to characterize the prevalence of irritability among U.S. adults, and the extent to which it co-occurs with major depressive and anxious symptoms. A non-probability internet survey of individuals 18 and older in 50 U.S. states and the District of Columbia was conducted between November 2, 2023, and January 8, 2024. Regression models with survey weighting were used to examine associations between the Brief Irritability Test (BITe5) and sociodemographic and clinical features. The survey cohort included 42,739 individuals, mean age 46.0 (SD 17.0) years; 25,001 (58.5%) identified as women, 17,281 (40.4%) as men, and 457 (1.1%) as nonbinary. A total of 1218(2.8%) identified as Asian American, 5971 (14.0%) as Black, 5348 (12.5%) as Hispanic, 1775 (4.2%) as another race, and 28,427 (66.5%) as white. Mean irritability score was 13.6 (SD 5.6) on a scale from 5 to 30. In linear regression models, irritability was greater among respondents who were female, younger, had lower levels of education, and lower household income. Greater irritability was associated with likelihood of thoughts of suicide in logistic regression models adjusted for sociodemographic features (OR 1.23, 95% CI 1.22–1.24). Among 1979 individuals without thoughts of suicide on the initial survey assessed for such thoughts on a subsequent survey, greater irritability was also associated with greater likelihood of thoughts of suicide being present (adjusted OR 1.17, 95% CI 1.12–1.23). The prevalence of irritability and its association with thoughts of suicide suggests the need to better understand its implications among adults outside of acute mood episodes.