Depression is a common mental disorder and is associated with work disability. For the implementation of evidence-based interventions, such as Individual Placement and Support (IPS) for people with depression in Germany, the aim of this study was to investigate client variables that predict return to work. The sample consisted of 129 participants, initially treated in a psychiatric hospital due to major depression, who participated in IPS as part of a German clinical trial. Baseline demographic (age, sex, education, sickness absence days, employment status), psychiatric (symptom severity, comorbidity, general physical and mental health, disability), and neuropsychological (self-rated deficits, test performance) variables were included. Return to work within one year was predicted using separate and overall binary logistic regression analyses. A total of 70 participants (56 %) returned to work within the one-year follow-up period. >100 days of sick leave in the year prior to study entry (vs. <100 days) and higher self-rated cognitive deficits were significantly associated with reduced odds of return to work within one year of IPS. The sample consisted of participants with a relatively good work history who were assigned to IPS by the treatment team, thus, the generalizability of the results is limited. People with depression who participate in IPS interventions might benefit from specifically targeting perceived cognitive deficits. Factors associated with prolonged sick leave due to depression and their role in return to work with IPS need further investigation. •Studying supported employment outcomes of participants with depression•56 % of the participants returned to work within one year•Longer duration of sick leave significantly decreased odds of return to work•More perceived cognitive deficits significantly decreased odds of return to work