The effects of graywater irrigation on soil chemical properties, and the accumulation of surfactants and antimicrobials, were investigated at three households in Arizona, California, and Colorado over the duration of two to three years. No negative effects were observed, with respect to sodium and boron accumulation in soil, over the duration of this study. Graywater irrigation significantly increased organic matter and total inorganic nitrogen of the receiving soil (P < 0.05). Graywater loading rates and fertilizer application should be monitored to ensure that excessive amounts of nitrogen and phosphorus are not applied to the soil. Notable concentrations of antimicrobials were detected in surface soil samples. It is suggested that the effect of antimicrobials on soil microbial health, and the potential for formation of antibiotic-resistant genes, be further investigated. Surfactant concentration in soil samples substantially increased after graywater application, compared with baseline samples, and then remained fairly constant over time.