Objectives: Clinical practice guidelines recommend questionnaires with short recall. We compare responsiveness of ecological momentary assessments (EMAs) and retrospective assessments of thyroid-related quality of life. Study Design and Setting: Patients with newly diagnosed thyrotoxicosis completed retrospective Thyroid-related Patient-Reported Outcome measures (ThyPROs) with 4-week and 1-week recall, respectively, and three daily EMAs for 4 weeks at time of inclusion and again after treatment (N = 115). Magnitude of change and statistical power (F-test statistics) were compared. Two designs were applied to the same data: Design 1 mimicked the practical realities of clinical trials by comparing 4-week recall ThyPRO administered at time of inclusion with EMA initiated at time of inclusion and collected prospectively for 1 week, thus not covering the same time frame or duration. Design 2 compared assessments covering the same 4 weeks after inclusion. Results: Design 1: the estimated change and statistical power were significantly larger for 4-week ThyPRO compared with EMAs. Design 2: retrospective assessments and EMAs had comparable change and power. Repeated 1-week ThyPRO administrations increased the statistical power. Conclusion: Selecting the optimal time frame for evaluation proved crucial for responsiveness. EMAs did not provide higher responsiveness than retrospective measures in either design. Repeated 1-week ThyPRO administrations increased statistical power.