Washing is an essential postharvest processing step for reducing microbial populations, tissue latex fluids, and soil on fresh and fresh-cut produce. This study focuses on the performance of a novel in-flight washer (IFW) in which produce falls through a round vertical canister, equipped with an array of nozzles near its interior boundary, spraying a sanitizing liquid upward and radially inward so as to directly impact the falling produce. The spray retards downward motion of the produce, while reorienting it as it falls, thus improving contact between liquid and produce. Chopped iceberg lettuce was passed through an IFW, a flume system, or sequentially through both, with different free chlorine levels. Microbial reduction and quality parameters (sensory attributes and tissue membrane integrity) were evaluated on days 0, 7, and 14 of a 14-day storage period. When washed only in the IFW with 200 mg/L free chlorine (FC), 1.0 and 1.4 log reductions of inoculated E. coli were achieved on Days 0 and 14, respectively. These reductions are comparable to or greater than those achieved with only flume washing at 20 mg/L FC. Among all treatments, washing in IFW at 200 mg/L FC resulted in the lowest aerobic plate count and yeast and mold values, as well as the highest overall quality score. These results indicate that use of the IFW can improve postharvest food safety and quality of fresh-cut lettuce, compared to conventional flume washing.