Objective: Second-generation antipsychotics may enhance the rehabilitation of individuals with schizophrenia. The authors hypothesized that clients receiving second-generation antipsychotics would use vocational rehabilitation services more effectively and would have better employment outcomes than those receiving first-generation antipsychotics. Methods: Ninety unemployed clients with schizophrenia and related disorders who were beginning a vocational rehabilitation program were followed for nine months. Three groups were defined according to the medication in use at study entry: olanzapine (N=39), risperidone (N=27), or first-generation antipsychotics only (N=24). Participants were interviewed monthly. Results: The olanzapine and risperidone groups did not differ on any employment outcomes. On most vocational indicators, clients receiving second-generation agents did not differ from those receiving first-generation agents. However, at nine months the second-generation group had a significantly higher rate of participation in vocational training; a trend was found toward a higher rate of paid employment. All groups showed substantial improvement in employment outcomes after entering a vocational program. Conclusions: The hypothesis that second-generation antipsychotics promote better employment outcomes than first-generation antipsychotics was not upheld. However, second-generation agents appear to be associated with increased participation in vocational rehabilitation.