OBJECTIVES: This study compares the risks of side effects [SE] associated with a broad of range of typical and atypical antipsychotics used to treat patients with schizophrenia.  METHODS: Medical and pharmacy claims data from Humana from January 2007 to June 2013 were used to define episodes of antipsychotic drug therapy for patients with schizophrenia.  Episodes were screened for a minimum of 180 days of pre-episode and 360 days of post-episode data, and for the existence of study SEs prior to the episode index date.  Study samples ranged from N=97,481 for rhabdomyolysis (RM) to N=99,017 acute urinary retention (AUR).  Other SE for analysis included acute kidney injury (AKI), hypotension, pneumonia (PNA), acute coronary syndrome (ACS) or ischemic stroke/cerebral infarction, and ventricular cardiac arrhythmia (VCA).  Logistic regression models were used to estimate the impact of alternative antipsychotics on the risk of an emergent SE in the year following the initiation of treatment.  The logistic models controlled for patient demographics, treatment history, concomitant use of antidepressants, mood stabilizers and anticonvulsants, and diagnostic and drug use profiles in the prior 6 months.  Haloperidol was used as the comparison drug. RESULTS: Perphenazine and ziprasidone reduced the risk of acute cardiovascular events relative to haloperidol.  The risk of acute kidney injury was significantly increased in patients taking aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone relative to haloperidol. The risk of hypotension was elevated in chlorpromazine and quetiapine patients and reduced in those using paliperidone, perphenazine and thiothixene.  The risk of AUR was increased in patients using fluphenazine, but reduced in patients using aripiprazole, risperidone and thiothixene.  The risk of RM was increased by the use of fluphenazine and quetiapine while the risk of pneumonia was elevated for patients using chlorpromazine, clozapine, paliperidone and quetiapine.  CONCLUSIONS: The risk of side effects varies widely across antipsychotic medications.