Background: Case observations imply that depressed patients with mixed features are of high risk for maniform switch during acute treatment. Methods: The medical records of 158 bipolar I depressives were examined with respect to mixed depressive features at admission, naturalistic medications, and maniform switch during inpatient treatment. Results: Besides pharmacological variables, the number of mixed depressive symptoms (flight of ideas, racing thoughts, logorrhea, aggression, excessive social contact, increased drive, irritability, and distractibility) at admission was associated with a higher risk for, and the acceleration of, maniform switch during inpatient treatment. Limitations: This was a retrospective study in patients receiving naturalistic treatment. The cohort was hospital based and thus not representative of the full range of bipolar affective disorder. Conclusions: In line with recent studies, our results underline the factors inherent in subjects at a higher risk of switch. Investigation of the relationships between several inherent factors and their interactions with pharmacological treatments may be important in resolving the controversy surrounding antidepressant-induced mania. Further validation studies on mixed depression are warranted.