Objective: To determine trends in rates of nosocomial infections in Spanish hospitals.Design: Prospective prevalence studies, performed yearly from 1990 through 1994.Setting: A convenience sample of acute-care Spanish hospitals.Participants and Patients: The number of hospitals and patients included were as follows: 1990, 125 hospitals and 38,489 patients; 1991, 136 and 42,185; 1992, 163 and 44,343; 1993, 171 and 46,983; 1994, 186 and 49,689. A core sample of 74 hospitals, which participated in all five surveys and included a mean of 23,871 patients per year, was analyzed separately.Results: The overall prevalence rate of patients with nosocomial infections in the five studies was as follows: 1990, 8.5%; 1991, 7.8%; 1992, 7.3%; 1993, 7.1%; and 1994, 7.2%. The prevalence rate of patients with nosocomial infection in the core sample of 74 hospitals was 8.9%, 8.0%, 7.4%, 7.6%, and 7.6%, respectively (test for trend, P=.0001). Patients admitted to intensive care units had a 22.8% prevalence rate of nosocomial infection in 1994. The most common nosocomial infections by primary site were urinary tract infection and surgical site infections, followed by respiratory tract infections and bacteremia. More than 60% of all infections were supported by a microbiological diagnosis.Conclusions: The EPINE project provides a uniform tool for performing limited surveillance of nosocomial infections in most Spanish acute-care hospitals. Its use helps to spread an accepted set of definitions and methods for nosocomial infection control in the Spanish healthcare system. The surveys indicate that the prevalence of nosocomial infections has been reduced over the last 5 years in a core sample of Spanish hospitals.