This paper presents a calibration and thermal compensation method that aims to minimize cost and processing time while maintaining high accuracy. First, the number of positions to perform the calibration procedure is optimized, and then, based on this optimized calibration number, thermal compensation is performed, which is necessary for environments with large temperature variations, since calibration parameters change at different temperatures. The calibration procedures and algorithms were experimentally validated on marketed accelerometers. Based on the optimized calibration method, the calibrated results have been obtained nearly 100 times improvement. Thermal drift calibration experiments on the triaxial accelerometer show that the thermal compensation scheme in this paper can effectively reduce drift in the temperature range of -40°C to 60°C. The temperature drifts of x- and y-axes are reduced from -13.2 and 11.8 mg to -0.9 and -1.1 mg, respectively. The z-axis temperature drift is reduced from -17.9 to 1.8 mg. We have conducted various experiments on the proposed calibration method and demonstrated its capacity to calibrate the sensor frame error model (SFEM) parameters. Therefore, the MEMS sensors calibrated in this paper have certain engineering application values for tilt measurement.