Background While modern electronic data collection methods (e.g., computer touch-screen or web-based) hold much promise, most current studies continue to make use of more traditional data collection techniques, including paper-and-pencil administration and telephone interviews. The present randomized trial investigated the measurement properties of the EORTC QLQ-C30 under three different modes of administration (MOA's). Methods A heterogeneous sample of 314 cancer patients undergoing treatment at a specialized treatment center in Amsterdam were randomized to one of three MOA's for the QLQ-C30: paper-and-pencil at home via the mail, telephone interview, and paper-and-pencil at the hospital clinic. Group differences in internal consistency reliabilities (Cronbach's alpha coefficient) for the scale scores were compared. Differences in mean scale scores were also compared by means of ANOVA, with adjustment for potential confounders. Results Only one statistically significant, yet minor, difference in Cronbach's alpha between the MOA groups was observed for the Role Functioning scale (all 3 alphas >0.80). Significant differences in group means -after adjustment- were found for the Emotional Functioning (EF) scale. Patients completing the written questionnaire at home had significantly lower levels of EF as compared to those interviewed via the telephone; EF scores of those completing the questionnaire at the clinic fell in-between those of the other two groups. These differences, however, were small in magnitude. Conclusions MOA had little effect on the reliability or the mean scores of the EORTC QLQ-C30, with the possible exception of the EF scale.