OBJECTIVES To assess the impact e-system use has on a provider's prescribing of low cost generic drugs through lower costing channels. METHODS Generic/brand, mail/retail, and cost-per-day (costs) for over nine million adjudicated prescriptions dispensed between July 2002 and December 2005 were incorporated into independent multivariate logistic and general linear models to compare prescriptions from 468 providers prescribed before and after using an e-system and 28,734 "no use"(control) providers. Separate models for ACE Inhibitors, ARB and ARB Combinations, H2 Antagonists, HMG Inhibitors, NSAIDs, PPIs, and SSRIs classes included independent variables for: provider degree, specialty, and e-system use (no, little and regular use prescribed > 50 prescriptions/month); patient sex, age (continuous), and regimen status; claim month and distribution channel (except in mail/retail models). Significance was a p-value≤0.01. RESULTS Generic and mail prescriptions were generally more likely to be prescribed from providers with regular use (ORs: 0.80"C1.20) and less likely from those with little or no use (ORs: 0.65"C1.23) than prescriptions from the pre-period of providers who became regular users (OR=1.00), with most significant and few exceptions. Costs were generally lower for providers with regular use (CEs: $-0.33"C$0.04) and higher for providers with little or no use (CEs: $-0.13"C$0.14) than prescriptions from the pre-period of providers who became regular users (CE=$0.00), with some significant and some exceptions. CONCLUSIONS Similar underlying patterns found across multiple classes provide support for linking regular use of e-systems to providers being even more likely to prescribe generics drugs and having them dispensed through mail, both of which likely lower overall costs. Additional research should be performed to better assess the robustness of these finding as participation expands and in more therapeutic classes.