Spindles are key components of machine tools. An efficient estimation of the spindle condition and its prognosis can improve production efficiency and quality due to predictive maintenance planning. This paper proposes a method for predicting the remaining useful life (RUL) of machine tool spindle bearings using a combined calculation and experimental approach. The calculation model based on the ISO 281 standard uses monitored real loading conditions caused by the machining process and the machine tool operation. The model enables the updated calculation of the spindle lifetime L10h using real load distribution. Since the operation hours of the spindle are also monitored, the remaining useful life (RUL) of the spindle can be calculated. This RUL value is corrected using a bearing condition assessment based on the effective value of the vibration velocity RMS according to the ISO 20816 standard and measured data from the machine tool control system. The proposed method is tested on two different spindle types featuring three pieces of every type. The experimental results of six spindles are compared and validated with a concurrent blind evaluation conducted by a skilled expert. The validation shows a very good match of the proposed method and the expert opinion. The method combining a calculation of the spindle lifetime using monitored real load distribution and subsequent result correction using vibration signal enables the implementation of a full automated estimation of the spindle RUL.