BACKGROUND Prescription review by pharmacists prior to dispensing is an important step in an overall strategy for preventing medication errors. Contacts with prescribers may be required to clarify missing, unclear, or inconsistent information. While essential to reduce the likelihood of potential patient harm, clarification contacts are time-consuming for pharmacists and prescribers. The scope of the issue and the factors that contribute to it are not well understood. OBJECTIVE To quantify the frequency of contacts with prescribers that were necessary to obtain clarification of prescriptions and to identify the factors that made these prescriber contacts necessary. METHODS An analysis was conducted involving new prescriptions received by a national mail-order pharmacy that required clarification contacts with prescribers for quality reasons (i.e., those potentially impacting the accuracy of dispensing). Excluding refills and renewals, the percentage of new prescriptions requiring clarification contacts was calculated and categorized by incoming delivery channel (mail, fax, telephone, etc.). The quality problems that prompted these contacts were categorized according to the problem identified. RESULTS Among the total of 295378 new prescription orders received during the 1-week study period (from April 7 to April 13, 2002), 8.7% contained quality problems that necessitated clarification contact with prescribers. Prescriptions received by fax transmission and mail were most likely to require clarification as compared with direct telephone conversation and miscellaneous (including electronic) channels. Among prescriptions that required a clarification contact for quality problems, an average of 2.4 problems per prescription was observed. The most common problems were: directions unclear or missing (24.3%); refill quantity unclear, missing, or incorrect (24.3%); dosage unclear (20.2%); drug name or strength unclear (13.2%); missing physician or patient data (11.4%); and missing prescriber signature (3.2%). CONCLUSION Prescriber clarification contacts are frequently needed to reduce the potential for medication error in the current prescription fulfillment process. While these contacts are necessary to clarify data elements essential to accurate medication dispensing, they are time- and resource-intensive. These study results suggest that alternate prescription order channels, including electronic, could reduce the sizable burden of prescription order clarification in mail-order pharmacy.