The abuse of prescription opioids imposes a substantial public health and economic burden. Recent research using administrative claims data has substantiated the prevalence and cost of opioid abuse among commercially insured individuals. Although administrative claims data are readily available and have been used to effectively answer research questions about the burden of illness for many different conditions, an important issue is the reliability, replicability, and generalizability of estimates derived from different databases. Therefore, this study sought to assess whether the findings of a recently published study of opioid abuse in a commercial claims database (original analysis) could be replicated in a different commercial claims database. The original analysis, which analyzed the prevalence and excess health care costs of diagnosed opioid abuse in the OptumHealth Reporting and Insights Database, was replicated by applying the same approach to the Truven MarketScan Commercial Claims and Encounters Database (replication analysis). In the replication analysis, the prevalence of diagnosed opioid abuse increased steadily from 15.8 diagnosed opioid abusers per 10,000 in 2009, to 26.6 diagnosed opioid abusers per 10,000 in 2012. Although the prevalence of diagnosed opioid abuse was higher than reported in the original analysis, the trend of increasing prevalence over time was consistent across analyses. Additionally, diagnosed abusers had excess annual per patient health care costs of $11,376 in the replication analysis, which was consistent with the excess annual per patient health care costs of diagnosed abuse of $10,627 reported in the original analysis. The replication analysis also found an upward trend in the prevalence of diagnosed opioid abuse over time and substantial excess annual per patient health care costs of diagnosed opioid abuse among commercially insured individuals, suggesting that these findings are generalizable to other commercially insured populations.