ABSTRACT Impact microindentation (IMI) is a technique to assess bone material properties of the cortical bone at the tibia in a transcutaneous, microinvasive, way. IMI is increasingly used in studies evaluating the contribution of tissue material properties to bone fragility in humans, and is approved for use in the clinic in Europe and the United States. Previous data show that IMI is well tolerated during and immediately after the procedure. The aim of this prospective observational study was to evaluate the longer‐term safety and acceptability of an IMI measurement using the handheld OsteoProbe device®. Included were patients who were scheduled for a measurement at the Leiden University Medical Center from September 2019 to December 2020 and willing to participate. Patients were asked to review the procedure right after the measurement, and by telephone interviews 1 week and 1 month thereafter. The primary outcome was the 30‐day complication rate after the measurement. Included were 106 patients (71 women) with a median age of 59 years (range, 20 to 86 years). Only three minor events were reported by 1‐week follow‐up, with an overall 30‐day event rate of 2.8%. These were a very small hematoma in two patients, and a small bruise in one patient, all of which resolved without medical intervention. No other safety‐related concerns were observed, and all 106 patients would undergo the measurement again if needed. The vast majority had no pain at baseline, 1‐week and 1‐month follow‐up (80.2%, 88.4% and 94.3%, respectively). In this first and large longitudinal study we demonstrated that although minimally‐invasive, IMI using the OsteoProbe® device at the tibia did not lead to any complications, and was well accepted by patients. Results strongly suggest that IMI can be safely used in studies as well as in the clinic in the hands of an experienced operator. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.