Aim 1 of this cross-sectional, observational study with people in residential treatment for substance use disorders (SUDs) was to document stress exposure. Aim 2 was to assess potential sociodemographic and health differences based on probable posttraumatic stress disorder (PTSD) status. Aim 3 was to assess relative contributions of Diagnostic and Statistical Manual (DSM)-congruent versus DSM-incongruent stressors (Criterion A vs non-Criterion A) to mental and physical health. We hypothesized that both types of stressors would significantly contribute to impairment across indicators and that DSM-congruent stressor exposure would be more strongly associated with impairment than DSM-incongruent exposure. We assessed exposure to DSM-congruent traumatic stressors and DSM-incongruent life stressors, PTSD and depressive symptoms, emotion regulation difficulties, substance use recovery capital, and physical/mental health-related quality of life among 136 people in residential SUD treatment who were 64% men, 36% women; 49% white, 41% Black, 11% multiracial/another race; 18% lesbian, gay, or bisexual (LGB+); mean age = 39.82 (standard deviation = 12.24) years. Participants reported experiencing a mean of 9.76 (SD = 6.11) DSM-congruent events. Those with probable PTSD were younger and more likely to be LGB+ than those without probable PTSD (P < .05). Experiencing higher numbers of DSM-congruent events was associated with more severe PTSD and depressive symptoms, emotion regulation difficulties, and lower physical health-related quality of life (P < .05). DSM-incongruent stressor exposure was not independently associated with any indicators. Recovery capital was not associated with either type of stress exposure. Stressful event exposure among people in residential SUD treatment is very high. Those who are younger or LGB+ in residential SUD treatment may be at greater risk of developing PTSD. DSM-congruent stressors are more consistently associated with mental health indicators than are DSM-incongruent stressors. Prioritizing treatment targets and identifying implementable treatment strategies can be challenging with this complex population.