Efficacy of nisin-EDTA treatments as a sanitizing treatment for reducing native microflora of whole melons and extending shelf-life of fresh-cut pieces was compared to chlorine treatments. Whole cantaloupe and honeydew melons were washed with water, nisin (10 μg/mL)-EDTA (0.02 M), or 200 ppm chlorine for 5 min at ∼ 20C before fresh-cut preparation and storage at 5C for 15 days with periodic microbiological sampling. In addition, some fresh-cut pieces were washed with 10 μg/mL nisin-EDTA or 50 ppm chlorine for 1 min before storage. Changes in appearance, odor, overall acceptability and the shelf-life of the minimally processed fresh-cut melons were investigated. Preliminary studies indicated that water washes, EDTA (0.002 to 0.2 M) or nisin (5 to 10 μg/mL) were not effective in reducing the microflora of whole melon when used individually. Nisin-EDTA and chlorine treatments were significantly (P < 0.05) more effective in reducing native microflora than water washes. Nisin-EDTA treatments were significantly (P < 0.05) more effective than chlorine in reducing populations of yeast and mold and Pseudomonas spp. on whole melon surfaces but were not as effective as chlorine treatments for reducing aerobic mesophilic bacteria, lactic acid bacteria and total gram-negative bacteria. Microbial contaminants on fresh-cut pieces washed with 50 ppm chlorine or nisin-EDTA were further reduced. However, microbial populations increased throughout refrigerated storage irrespective of treatments. Odor, appearance, and overall acceptability ratings for cantaloupe and honeydew fresh-cut pieces treated with nisin-EDTA or chlorine were not significantly (P > 0.05) different from each other throughout the storage period (15 to 21 days). However, both treatments led to significantly (P < 0.05) improved ratings compared to the controls for the fresh-cut pieces at 9 to 12 days of storage and thereafter. The results of this study suggest that treatments with nisin-EDTA before and after fresh-cut processing would improve the quality and extend the shelf-life of fresh-cut melon.