BACKGROUND: The Hyperhidrosis Quality of Life Index (HidroQoL©) is a well-developed patient-reported outcome measure assessing the quality of life impacts in hyperhidrosis (HH), which has proven very good measurement properties, such as structural validity and internal consistency. OBJECTIVES: We aimed to investigate responsiveness over time and estimate values for meaningful within-person change (MWPC) towards symptom improvement for different measurement timepoints (4 and 12 weeks), extending the existing validity evidence in patients with primary axillary HH. METHODS: Data (from a phase IIIb clinical trial) were collected at baseline, and at weeks 4, 8, 12, 28, 52 and 72. For the assessment of responsiveness, HidroQoL change scores were correlated with corresponding change scores of the Hyperhidrosis Disease Severity Scale (HDSS), the Dermatology Life Quality Index (DLQI) and gravimetric sweat production based on a priori formulated hypotheses. Furthermore, we tested whether the different HDSS change score groups differed significantly from each other over time and whether the HidroQoL was sensitive towards these group differences over time. This was extended by the calculation of matched-pair tests and effect sizes to test significance for each change group separately. For the estimation of MWPC thresholds towards symptom improvement, different anchor-based and integrated approaches were used. RESULTS: In total, the sample comprised 357 patients with primary axillary HH. For the assessment of responsiveness, five out of 14 a priori hypotheses regarding the correlation of the change scores could be confirmed, whereas the rejected hypotheses differed only marginally from the expected values. Furthermore, regarding responsiveness, the HidroQoL showed sensitivity towards symptom improvement at each measurement timepoint. Effect sizes were large as expected (d ≥ 0.806). MWPC thresholds towards symptom improvement were proposed for two measurement timepoints: 5 (week 4) and 6 (week 12). Increasing MWPC values over time were observed. CONCLUSIONS: This study extends the evidence for the longitudinal validity of the HidroQoL© up to 72 weeks and proposed MWPC thresholds for different time intervals (4 and 12 weeks) after baseline, aiding interpretability. Results concur with findings from previous validation studies.