To provide meat processors with data to assess the safety of cooked ready-to-eat roast beef production parameters, a study was conducted to determine the contribution of humidity to the lethality of salmonellae during thermal processing. Destruction of Salmonella during thermal processing at different levels of humidity and a constant cooking temperature of 82.2°C was examined. Raw beef top round roasts purchased from a commercial supplier were inoculated with a seven-strain cocktail of heat-shocked Salmonella. Inoculated roasts were thermally processed to an internal temperature of 62.8°C at 0 to 90% humidity. Salmonella counts were determined utilizing the thin agar layer method on xylose-lysine-desoxychlolate agar to facilitate the enumeration of injured cells. Significant differences (P < 0.05) in Salmonella counts were observed between roasts processed at 30% humidity and those processed at 15% humidity or lower. Salmonella reductions were less than the regulatory performance standard of 6.5 log units at a humidity of <30%. These results indicate that cooked ready-to-eat roast beef can be safely processed under conditions outside of the U.S. Department of Agriculture (USDA) Food Safety and Inspection Service "safe harbor" guidelines. However, the results also indicate that one of these current safe harbor guidelines for the production of cooked ready-to-eat roast beef (≥62.8°C product internal temperature with humidity introduced for ≥50% of the cooking cycle) could result in a finished product that does not meet USDA performance standards. This specific guideline should be clarified with a minimum relative humidity requirement to ensure the production of a safe product.