It is far from clear how comorbidity changes during alcoholism treatment. This study investigates: (1) the course of comorbid Axis I disorders in chronic alcoholics over 2 years of controlled abstinence in the outpatient long-term intensive therapy for alcoholics (OLITA) and (2) the effect of comorbid Axis I and II disorders in this group of patients on subsequent drinking outcome over a four-year follow-up. This prospective treatment study evaluates psychiatric variables of 89 severely affected chronic alcohol dependent patients on admission (t(1)), month 6 (t(2)), 12 (t(3)) and 24 (t(4)). Drinking outcomes have been analyzed from 1998 to 2002. On admission, 61.8% of the patients met criteria for a comorbid Axis I disorder, 63.2% for a comorbid personality disorder. Axis I disorders remit from t(1) (59.0% ill), t(2) (38.5%), t(3) (28.2%) to t(4) (12.8%) (p < 0.0001). Anxiety disorders remit more slowly from t(1) (43.6%) to t(3) (20.5%, p = 0.0086), whereas mood disorders remit early between t(1) (23.1%) and t(2) (5.1%, p = 0.0387) with a slight transient increase at t(3) (10.3%). During the four-year follow-up, the cumulative probability of not having relapsed amounts to 0.59. Two predictors have a strong negative impact on abstinence probability: number of inpatient detoxifications (p = 0.0013) and personality disorders (p = 0.0106). The present study demonstrates a striking remission of comorbid Axis I disorders upon abstinence during comprehensive long-term outpatient alcoholism treatment. The presence of an Axis II rather than an Axis I disorder on admission strongly predicts drinking outcome over a four-year follow-up.