This study aims to determine the effect of bone surface macro-groove preparation on the strength of the bone-cement interface. Polymethyl methacrylate (PMMA) was considered as bone cement, and cancellous bone was extracted from the bovine femur to prepare the bone-cement specimen. A total of seventy-eight (78) bone-cement specimens were prepared, which consist of different shapes of the groove, size of groove, number of grooves, and distance between two grooves (pitch distance) and tested using the universal testing machine (UTM) by applying mode-II and mixed-mode (mode-I + mode-II) loading. Rectangular and semi-circular shape grooves were considered to determine the effect of the shape of the groove on the strength of the bone-cement interface. For semi-circular grooves, single and double semi-circular grooves with two different sizes (4 mm and 6 mm) were considered. In the double semi-circular groove, apart from two different sizes (4 mm and 6 mm), two different pitch distances (8 mm and 9 mm) between two grooves were considered to understand the effect of pitch distance on bone-cement interfacial strength. Bone-cement interfacial strength was measured in terms of the maximum load, energy absorbed before failure, and strength of the bone-cement specimen. Results indicated that rectangular grooves performed better in terms of strength; however, local cancellous bone failure was observed, which restricted the use of rectangular grooves for bone-cement fixation. Maximum load, energy absorbed before failure, and strength of the bone-cement specimen were found to be increased as the size, pitch distance, and the numbers of the groove increases. Results of our study also indicated that a single large groove at the bone-cement interface was found to be more effective than the two small grooves to increase the strength of the bone-cement interface. Apart from these, pitch distance also plays an important role in increasing the strength of the bone-cement interface.