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Jackfruit skin (Artocarpus heterophyllus) is known to containflavonoid, alkaloid, tanin/fenolik, saponin, and terponoid. Escherichia coli is one example of bacteria that cause disease in the human body. The purpose of this study was to determine the antibacterial activity of ethanol extract of jackfruit skin against Escherichia coli. Stages of the study began with extraction of jackfruit skin using maceration method and 70% ethanol solvent. Antibacterial activity was tested using the disk diffusion method (Kirby-Bauer) with ethanol extract concentrations of 60% and 80%, positive control used cotrimoxazole and negative control used ethanol 70%. Inhibition zone measurement results Jackfruit skin extract with a concentration of 60% and 80% respectively 14.3 mm, 15.3 mm. Cotrimoxazole on Escherichia coli bacteria of 15.3mm can be concluded that Jackfruit skin extract has antibacterial activity in the strong category against Escherichia coli bacteria. This is based on statistical analysis using Escherichia coli One Way ANOVA with a significance value of more than 0.05. This shows that the data obtained were normally distributed so that it was continued with One way ANOVA. Based on these tests have a significance of more than 0.05 which means there is no significant difference in the inhibition zone as a result of differences in concentration of jackfruit skin extract.