Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) frequently co-occur. However, little is known about the importance of their temporal order of onset. In this study, differences in clinical presentation and response to cognitive-behavioral substance use therapy by order of onset were examined among 94 (51 men, 43 women) treatment-seeking individuals with AD and comorbid PTSD. Participants were interviewed, completed a battery of assessments, and received 12 weeks of individual, manualized psychotherapy. The findings revealed that women were more likely than men to have primary PTSD (i.e., the onset of PTSD preceded the onset of AD). At treatment entry, women with primary AD and men with primary PTSD presented as more distressed and/or depressed, as compared to their counterparts. Individuals with primary PTSD reported a more extensive trauma history than individuals with primary AD. Examination of treatment response revealed that the majority of individuals in the study demonstrated significant improvements in PTSD and AD symptomatology. A relationship between increased alcohol intake and higher PTSD symptom levels was observed. In general, the primary PTSD group appeared to derive greater overall benefit from this form of therapy (e.g., greater improvement in physical health, alcohol use, social functioning), as compared to the primary AD group. Finally, women with primary AD appeared particularly vulnerable to continued psychiatric distress and depression at the end of treatment. These findings increase awareness of the importance of considering the order of onset, the heterogeneity among this dual diagnosis, and may ultimately lead to improvements in treatment design.