The purpose of this study was to describe the epidemic of clinically apparent human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection in Nicaragua and to discuss the reasons why the number of HIV patients presenting to the public health care system is increasing compared with other Central American countries. From 1987 to 2004, 1,614 HIV-positive patients were officially reported to the Nicaraguan STI/HIV/AIDS national program. Urban areas along the west-central and eastern part of Nicaragua showed the highest prevalence of AIDS, with a maximum of 54.2/year per 100,000 inhabitants. Most of the infections (91%) were acquired sexually: 65% by heterosexual contacts and 26% by homosexual contacts. The highest rate of infection was found in men aged between 20 to 39 years, with a peak around 35 to 39 years (annual incidence of 125.6 new cases per 100,000 inhabitants), and in women aged 20 to 34 years old, with a peak around 20 to 24 years (annual incidence 46.6 per 100,000 inhabitants). The male to female ratio of infection was 3:1. The death rate was stable until the beginning of 1999, but increased sharply thereafter up to 2004, the year that highly active antiretroviral therapy (HAART) was introduced in Nicaragua. In 2005, we observed a further increase in the mortality. However, our data do not represent the magnitude of the HIV/AIDS epidemic as a whole, due to a lack of systemic surveillance. HIV/AIDS in Nicaragua is in a nascent stage and is concentrated in high-risk populations, such as utility workers, commercial sex workers, men who have sex with men, prisoners, street children, housewives and police and military forces. Education of the population is an urgent need to increase HIV/AIDS-related knowledge, change attitudes, and increase safer sex practice in the community.