The survival curves of two strains of Escherichia coli (ATCC 4157 and ATCC 23716) were obtained by high hydrostatic pressure (HHP) at four pressure levels (100, 200, 300, and 400 MPa) in an orange juice-skim milk (OJ-SM) mixed beverage. The effect of suspension medium pH on HHP inactivation was studied at three pH levels: 4, 4.5, and 5. The Weibull model provided an accurate fit to the data according to adjusted-regression coefficients (adjusted-R(2)) [0.860-0.996], root mean square error values [0.001-0.150], and accuracy factor [1.001-1.125] values. For sensitivity analysis, Monte Carlo simulation was run to determine the most influential factors affecting HHP inactivation of E. coli strains. According to these results, the most influential factor for E. coli (ATCC 4157) HHP inactivation was the pH of the OJ-SM beverage at low HHP intensity, whereas pressure was more influential under strong HHP treatment conditions. Concerning E. coli K-12 (ATCC 23716), pressure (P) was the most influential parameter independently of the pH of OJ-SM beverage. The higher the P, the higher the inactivation achieved. The sensitivity analysis indicated greater E. coli K-12 (ATCC 23716) resistance to the HHP processing, possibly because of greater acidity tolerance.