Background This is a six-year prospective follow-up of a former cross sectional study of suicide attempters in a sample of treatment-seeking substance-dependent patients. The aims were to explore the frequency of patients with new suicide attempts (SA) during the six-year observation period, and to explore the predictive value of lifetime Axis I and II disorders, measured at index admission, on SA in the observation period, when age, gender and substance-use variables, measured both at admission and at follow-up, were controlled for. Methods A consecutive sample of 156 alcohol-dependent and 131 poly-substance-dependent inpatients and outpatients in two Norwegian counties were assessed at index admission (T1) with the Composite International Diagnostic Interview (Axis I disorders), Mon's Clinical Multiaxial Inventory (Axis II disorders) and Hopkins Symptom Checklist-25 (mental distress). At follow-up six years later (T2), 56% (160/287 subjects, 29% women) were assessed using the HSCL-25 and measures of harmful substance use (Alcohol Use Disorders Identification Test and Drug Use Disorders Identification Test). Results The prevalence of patients with SA between T1 and T2 was 19% (30/160), with no difference between sexes or between patient type (alcohol-dependent versus poly-substance-dependent). Sober patients also attempted suicide. At the index admission, lifetime eating disorders, agoraphobia with and without panic disorder, and major depression were significantly and independently associated with SA. Prospectively, only lifetime dysthymia increased the risk of SA during the following six years, whereas lifetime generalized anxiety disorder reduced the risk of SA. Individually, neither the numbers of Axis I and Axis II disorders nor the sum of these disorders were independently related to SA in the observation period. Substance use measured at T1 did not predict SA in the follow-up period, nor did harmful use of substances at follow-up or in the preceding year. Conclusion A high prevalence of SA was found six years later, both in patients still abusing substances and in sober patients. To prevent SA, treatment of both affective disorders and substance abuse is important.