In a relatively young sample of 108 nonbipolar patients with major depressive disorder and at least moderately severe depression, the contribution of a comprehensive set of socio-demographic, psychosocial, clinical and personality trait variables toward the prediction of short-term, multidimensionally evaluated response to tricyclic antidepressants was investigated by univariate and multivariate analyses. There is a naturalistic study without a standard treatment protocol, but treatment type, duration and dosage were controlled. Only patients who received at least moderate dosages of tricyclic antidepressants for minimum four weeks were included in this study. A relatively low number of predictors emerged. Initial severity of both symptoms and impairment of functioning were the most powerful predictors for all outcome criteria. Illness history was also relevant. Personality traits reflecting vulnerable personality style at the emotional and interpersonal level proved their predictive value. The combination of independent variables by multivariate regression analyses improve the prediction of treatment response.