Controversy exists concerning whether abuse of oxycodone will increase after the introduction of generic controlled-release (CR) oxycodone. We evaluated the effect of FDA approval of generic CR oxycodone on the misuse/abuse of oxycodone, hydrocodone, methadone and morphine utilizing data from eight poison control centers (PCC). PCC intentional exposure (IE) reason codes were used as measures of abuse. Opioid-specific quarterly IE rates (per 100,000 population and per 10,000 patients) were calculated for 1 year before and after approval (March 24, 2004). Changes in regression slopes (1 year before to 1 year after) and in IE rates (1 quarter before to 1 quarter after) were analyzed using Poisson regression. The regression slopes for oxycodone, methadone and morphine did not change after approval but decreased significantly for hydrocodone. None of the prescription opioids' IE rates significantly increased after approval. When changes in oxycodone's IE rates were compared to the other opioids, no statistically significant differences were found, indicating a lack of time-opioid interaction. These results did not vary when population rates or patient rates were used. PCC data indicate that approval of generic CR oxycodone was not followed by an immediate unfavorable effect on the misuse/abuse of oxycodone.