Sewage sludge production has significantly increased during the last years in European Union (EU) countries, being primarily used for agricultural purposes. In this study, digested sewage sludge was applied to greenhouse soil over a three-year period (2001–2003), with three sludge treatments in the first two years (2, 4, and 6 kg m−2) and three more applications using a greater quantity in the last year (6, 8, and 10 kg m−2). The effects of sewage sludge application on soil and on a leafy crop (Lactuca sativa L.) were studied. Mineral elements, organic matter, pH, and heavy metals were measured in soil and plant tissues. Pathogen and indicator microorganism dynamics in soil were also determined after each sludge application. Results showed that sewage sludge applications increased organic matter, P, and N Ca content in soil. Furthermore, Zn, Pb, Ni, and Cu content increased in soils, primarily after high doses of sludge. The highest yield value was obtained in the second-year harvest, since the last sludge application did not increase yield. Fecal coliform numbers decreased significantly one month after sludge application. However, total coliforms, Clostridium sulphite-reducers and Salmonella, were present in soils three months after sludge application.