Opposite to the fracture side, bone mineral density (BMD) measured by DXA at the contra-lateral side does not change after a distal radius fracture. However, it is unknown if also bone micro-architecture and strength at the contralateral side are unaffected. Therefore, the aim of this study was to assess BMD, micro-architecture and bone mechanical properties at the contra-lateral side during two years follow-up after a distal radius fracture using high resolution peripheral quantitative computed tomography (HRpQCT). The contra-lateral distal radius of 15 postmenopausal women (mean age 64 ± 8 years) with a distal radius fracture treated by cast immobilization was scanned by HRpQCT at baseline, 3 months and 2 years post-fracture. BMD and cortical and trabecular micro-architecture were measured and biomechanical parameters were estimated using micro finite element analysis (μFEA). Additionally, markers of bone resorption and formation were measured at each visit. Bone parameters and turnover markers across the three visits were analysed using a linear mixed-effect model with Bonferroni correction. Two years post-fracture, a significant decrease from baseline was found in cortical BMD (− 4.2%, p < 0.001), failure load (− 6.1%, p = 0.001), stiffness in compression (− 5.7%, p = 0.003) and bending (− 6.4%, p = 0.008), and bone formation (− 47.6%, p = 0.010). No significant changes from baseline were observed in total and trabecular BMD, nor in cortical or trabecular micro-architecture and neither in bone resorption. Results were similar between patients with or without adequate anti-osteoporosis drug treatment. We found a significant decline in BMD in the cortical but not the trabecular region, and a reduction in bone strength and stiffness at the contra-lateral side two years after a distal radius fracture. These changes exceeded the changes that may be expected due to aging, even in the presence of adequate anti-osteoporosis treatment.