Only few studies have compared the effects of Typical and Atypical Antipsychotics on Metabolic Syndrome (MS) onset. The present study examined in schizophrenic and bipolar patients the impact of haloperidol (mean dose 3.37±2.28 mg and 2.51±1.48 mg, respectively) and olanzapine treatment (mean dose 12.42±6.53 mg and 9.97±5.36 mg, respectively) on glycemia, blood pressure (BP), BMI, triglycerides, HDL cholesterol, fasting cholesterol and body weight (BW). Our data disclosed significant time x diagnosis x drug treatment interactions for fasting cholesterol (p<.005), systolic BP (p<.003), BW (p<.005) and BMI (p<.02) suggesting that these parameters differently changed overtime in the two groups in relation to the 2 drug treatments. Indeed, increases in fasting cholesterol, systolic BP, BW and BMI were significantly higher in olanzapine-treated patients as compared to haloperidol-treated ones and these effects were more pronounced in bipolar patients as compared to schizophrenic ones. Significant time x drug treatment interactions were found for fasting glucose and triglycerides (p<.0001), indicating that these parameters differently changed after the 2 drug treatments irrespective of the diagnostic group. Indeed, plasma levels of glucose and triglycerides significantly increased after olanzapine treatment but not after haloperidol in both patients groups.