BACKGROUND: Research in quality of life traditionally relies on paper-and-pencil questionnaires. Easy access to the Internet has inspired a number of studies that use the Internet to collect questionnaire data. However, Internet-based data collection may differ from traditional methods with respect to response rate and data quality as well as the validity and reliability of the involved scales. OBJECTIVE: We used a randomized design to compare a paper-and-pencil questionnaire with an Internet version of the same questionnaire with respect to differences in response rate and completeness of data. METHODS: Women referred for mammography at a Danish public hospital from September 2004 to April 2005, aged less than 67 years and without a history of breast cancer, were eligible for the study. The women received the invitation to participate along with the usual letter from the Department of Radiology. A total of 533 women were invited to participate. They were randomized to receive either a paper questionnaire, with a prepaid return envelope, or a guideline on how to fill in the Internet-based version online. The questionnaire consisted of 17 pages with a total of 119 items, including the Short Form-36, Multidimensional Fatigue Inventory-20, Hospital Anxiety and Depression Scale, and questions regarding social status, education level, occupation, and access to the Internet. Nonrespondents received a postal reminder giving them the option of filling out the other version of the questionnaire. RESULTS: The response rate before the reminder was 17.9% for the Internet group compared to 73.2% for the paper-and-pencil group (risk difference 55.3%, P < .001). After the reminder, when the participant could chose between versions of the questionnaire, the total response rate for the Internet and paper-and-pencil group was 64.2% and 76.5%, respectively (risk difference 12.2%, P = .002). For the Internet version, 97.8% filled in a complete questionnaire without missing data, while 63.4% filled in a complete questionnaire for the paper-and-pencil version (risk difference 34.5%, P < .001). CONCLUSIONS: The Internet version of the questionnaire was superior with respect to completeness of data, but the response rate in this population of unselected patients was low. The general population has yet to become more familiar with the Internet before an online survey can be the first choice of researchers, although it is worthwhile considering within selected populations of patients as it saves resources and provides more complete answers. An Internet version may be combined with the traditional version of a questionnaire, and in follow-up studies of patients it may be more feasible to offer Internet versions.