OBJECTIVES: To identify factors associated with primary nonadherence [PNA].   METHODS: This retrospective cohort study identified all new prescriptions written in an integrated health care system for 10 therapeutic drug groups over a three-month period (12/1/2009 - 2/28/2010).  Study drugs included: antiinfectives, analgesics, migraine medications, antidiabetics, osteoporosis medications, cardiovascular agents, antihyperlipidemics, antiasthmatics, antidepressants, and anticoagulants.  PNA was defined as the failure to fill a prescription within 14 days of when it was written.  Stepwise multivariable logistic regression was used to identify significant patient, provider and prescription characteristics associated with PNA.  RESULTS: A total of 569,095 new prescriptions were written for the study drugs of interest during the study period.  Across all drug groups, the PNA rate was 9.8%.  PNA rates for individual drug groups varied and were highest for osteoporosis medications (22.4%) and antihyperlipidemics (22.3%).  Patients were more likely to be primary nonadherent if they were black, were not prescribed any drug from the same therapeutic drug group during the past year, or had certain baseline comorbidities.  Also, patients who received brand name or multiple concomitant prescriptions were more likely to be primary nonadherent.  In contrast, patients who filled at least one prescription in the prior year, had dual insurance or Medicaid coverage, or had a prescription for a symptomatic disease were more likely to fill their prescription.  Patients who received prescriptions written by emergency medicine, pediatrics, or urgent care were less likely to be primary nonadherent.  Factors associated with PNA were mostly consistent across all drug groups, but the estimated direction and significance of some factors, such as patient gender and age, depended on whether the treatment was acute or chronic.  CONCLUSIONS: These results may be used to facilitate clinicians and payers in making informed decisions when designing and implementing cost-effective patient interventions to improve overall adherence to medications.