A novel, sensitive and selective stability-representing reverse phase Ultra performance liquid chromatography method was developed and validated for the quantitative determination of Erythromycin estolate in Erythromycin 250mg capsules. The chromatographic separation was achieved on BEH C18; 50 x 2.1mm; 1.7µm column by using mobile phase containing a mixture of 0.002M di-potassium hydrogen phosphate and acetonitrile 53:47 v/v at a flow rate of 0.6 ml/min. The column temperature was maintained at 40°C and detection were carried out at 210nm. To ascertain the stability-signifying ability of the method, drug product was subjected to strain conditions of acid, base, oxidative, hydrolytic, thermal, and photolytic degradation. The drug undergoes degradation at oxidative and thermal/humidity stress conditions. The resultant degrading peaks were well resolved from the drug peak. The drug was found to be stable in thermal and photolytic conditions. The urbanized method was validated as per ICH guidelines with respect to specificity, linearity, accuracy, precision, and robustness and the method show excellent linearity and a correlation coefficient of more than 0.99. Therefore, the projected method can be employed for the determination of Erythromycin estolate in various pharmaceutical formulations during regular and quality-control analysis.