The present study aimed to identify the prescribing patterns of lithium or of lithium+valproate in 75 bipolar I outpatients in a manic or a mixed phase within a naturalistic setting. The differences between the two treatments and the correlation between serum lithium levels and response were also examined. The results showed that patients with lithium levels of 0.60 mEq/l or more had higher remission rates and greater symptom reduction than the other patients. Patients on lithium and valproate showed greater improvement in mixed, anxiety, and psychotic symptoms than those on lithium only, as assessed by the Clinical Global Impression-Bipolar version scale scores. Finally, our findings suggest that a range of lithium levels between 0.40 and 0.60 mEq/l, albeit below the therapeutic range, seems sufficient to maintain a good effect when lithium is coadministered with valproate.