Abstract: In response to the stringent dimensional tolerance requirements of medium speed diesel engine blocks, such as positional accuracy, coaxiality, parallelism, perpendicularity, and surface roughness of multiple holes, an analysis was conducted based on the five key factors of the manufacturing process: personnel, machines, materials, methods, and environment. The main bearing bore was identified as the primary datum for the entire block, as it governs the machining of the cylinder liner bore, dual camshaft bores, and two bridge gear bores. Due to structural constraints and the size of accessory heads, secondary clamping was required. When re-establishing the coordinate system on the rotary worktable, a macro program was used to achieve one-time positioning, setting up four machining coordinate systems around the block to improve positioning accuracy. During machining, the roughing, semi-finishing, and finishing cycles of the fuel injection and intake/exhaust camshaft bores were monitored, as well as the elongation of accessory heads No.1 and No.2 every 30 minutes. A fifth-order polynomial least squares fitting method was applied to model their variation over time, enabling dynamic compensation. Finally, with bearing bores No.1 and No.8 used as measurement references, the measured deviations of multiple holes all met technical specifications, thereby achieving high-precision control of multi-bore machining in the medium speed diesel engine block.