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The first objective of this study was to examine the prevalence of prescriptions that offer the opportunity for generic drug use (a prescription for a multisource drug product). The second objective was to examine the prevalence of generic drug use by examining the rate of generic drug prescribing for multisource drug products and the rate of generic substitution by pharmacists. The last objective was to examine the association of prescriber, pharmacist, insurance, patient, and drug variables with the prescribing of drugs allowing the opportunity for generic drug use and generic substitution.A database containing information for 6380 prescription orders was used for analysis.Random-effects logistic regression panel data estimation was used to examine the association of independent variables with whether a prescription allowed the opportunity for generic drug use and whether a prescription allowing generic drug use and written using the brand name was generically substituted.The opportunity for generic drug use existed for 63% of prescription orders. Prescriptions covered by private third party and indemnity insurance were 33% (97.5% CI, 0.56–0.80), and 21% (97.5% CI, 0.62–0.98), less likely, respectively, to allow the opportunity for generic drug use relative to uninsured prescriptions. Unobserved prescriber characteristics accounted for 23% (95% CI, 0.14–0.34) of the variance in the opportunity for generic drug use. Pharmacists generically substituted 83.8% of prescriptions that could be generically substituted. Prescriptions covered by Medicaid were 4.57 (97.5% CI, 2.83–7.39), 5.15 (97.5% CI, 3.25–8.13), and 4.85 (97.5% CI, 2.83–8.17) times more likely, respectively, to be generically substituted relative to uninsured, private third party and indemnity prescriptions. Unobserved characteristics of pharmacists accounted for 44% (95% CI, 0.33–0.55) of the variance in the occurrence of generic substitution.Pharmacists play a large and important role in generic drug use and efforts to increase generic drug use directed at pharmacists should be maintained. Additional efforts to increase generic drug use likely should be targeted at prescribers.