A Novel stability indicating Reverse Phase-Liquid Chromatography (RP-HPLC) method has been developed and validated for the determination of Assay of Nintedanib Drug Substance in the presence of degradation products generated from forced degradation studies. Chromatographic separation was achieved on YMC Pack ODS-AQ (C18) column (Size: 250 x 4.6 mm; 5 μm particle size) at flow rate 1.0 mL/min. with 210 nm detection. The mobile phase was Water: Acetonitrile (pH of water was adjusted to 3.0 with Orthophosphoric acid) through gradient elution. Product was subjected to stress conditions like acid, base, peroxide, thermal and photolytic degradation. No new impurities were observed during thermal and Photolytic degradation. Two new impurities were observed during acid degradation, one impurity was observed in base degradation and another impurity was observed in peroxide degradation. However, degradation products did not interfere with the detection of Nintedanib. Developed method was validated as per ICH guidelines using validation parameters like specificity, linearity, LOQ, accuracy, precision, robustness and ruggedness. LOQ value was achieved at 2 μg/mL concentration. Good linearity (r2 > 1.00) was obtained ranging from 25 μg/mL to 150 μg/mL concentrations. Recovery was verified by spiking 40 μg/mL, 50 μg/mL and 60 μg/mL concentrated solutions to 50 μg/mL concentrated solution. Hence newly developed RP-HPLC method is capable for estimating assay of Nintedanib Drug Substance and the present method is effectively separated the Nintedanib from its major degradation products.