Magnesium orthopaedic fracture fixation devices can potentially provide significant clinical benefits, such as the elimination of secondary surgeries for device removal due to in-vivo resorption and reduced stress shielding due to reduced device stiffness. However, development, approval, and clinical adoption of magnesium devices has been hindered by the excessively high rates of in-vivo corrosion such that the structural integrity of the device can be catastrophically reduced before fracture healing occurs. Coating of devices with calcium phosphate coatings has been shown to significantly reduce corrosion rates, while enhancing osseointegration. However, the adhesion strength between the CaP coatings and magnesium substrates has not been previously investigated. Clinical insertion of fracture fixation devices such as intramedullary nails and k-wires will impose significant shear loading on the coated surface of the implant. If the effective shear strength of the coating-device interface is not sufficiently high, the coating will be damaged and removed during device insertion. In the current study a bespoke experimental-computational approach is developed to provide a new understanding of the relationship between coating thickness, surface roughness, and effective shear strength of the CaP coating- Mg substrate interface. Nine test cases were created by adjusting either the deposition time (3 thickness values) or the surface treatment of the Mg alloy using SiC paper (3 roughness values) and double-lap shear testing was performed for these coating configurations. Strain development in the Mg substrates was monitored using strain gauges, and failure stress was determined for each configuration. Test results revealed that the effective shear strength of the coating-substrate interface is significantly higher for coatings on the rougher substrate surfaces when compared to those on smoother surfaces. Coating thickness was not found to significantly influence the effective shear strength over the range considered in this study (0.37–1.34 μm). Micro-scale finite element models of lap-shear tests were constructed using experimental profilometry data. Simulations of rough coating-substrate interfaces reveal that significant localised compression occurs at the coating-substrate interface in regions of large asperities. A novel cohesive zone formulation has been developed to simulate compression induced shear hardening, and the resultant simulations are found to accurately predict the significantly higher effective shear strength measured experimentally for rougher coatings compared to smoother Mg substrate surfaces. Display omitted •Novel lap shear experiment studying the relationship between coating thickness, implant surface roughness and shear strength.•First cohesive zone model to incorporate shear hardening due to interface compression.•Regions of high interface compression at asperities in rough coatings, results in locally elevated interface shear strength.