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Background The study tests the effects of data collection modes on patient responses associated with the multi-item measures such as Patient-Reported Outcomes Measurement System (PROMIS®), and single-item measures such as Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Numerical Rating Scale (NRS) measures. Methods Adult cancer patients were recruited from five cancer centers and administered measures of anxiety, depression, fatigue, sleep disturbance, pain intensity, pain interference, ability to participate in social roles and activities, global mental and physical health, and physical function. Patients were randomized to complete the measures on paper (595), interactive voice response (IVR, 596) system, or tablet computer (589). We evaluated differential item functioning (DIF) by method of data collection using the R software package, lordif. For constructs that showed no DIF, we concluded equivalence across modes if the equivalence margin, defined as ± 0.20 × pooled SD, completely surrounds 95% confidence intervals (CI's) for difference in mean score. If the 95% CI fell totally outside the equivalence margin, we concluded systematic score difference by modes. If the 95% CI partly overlaps the equivalence margin, we concluded neither equivalence nor difference. Results For all constructs, no DIF of any kind was found for the three modes. The scores on paper and tablet were more comparable than between IVR and other modes but none of the 95% CI’s were completely outside the equivalence margins, in which we established neither equivalence nor difference. Percentages of missing values were comparable for paper and tablet modes. Percentages of missing values were higher for IVR (2.3% to 6.5% depending on measures) compared to paper and tablet modes (0.7% to 3.3% depending on measures and modes), which was attributed to random technical difficulties experienced in some centers. Conclusion Across all mode comparisons, there were some measures with CI’s not completely contained within the margin of small effect. Two visual modes agreed more than visual-auditory pairs. IVR may induce differences in scores unrelated to constructs being measured in comparison with paper and tablet. The users of the surveys should consider using IVR only when paper and computer administration is not feasible.