Many HIV-positive persons reportedly continue to engage in at-risk behavior. We compared the sexual and drug-using practices of HIV-positive persons before and after the diagnosis of HIV infection to determine whether their behavior had changed. To this end, in 2006, we conducted a cross-sectional study involving clinical centers in five Italian cities. Each center was asked to enroll 100 persons aged 18 years or older who had a diagnosis of HIV infection that dated back at least 2 years. Data were collected with a specifically designed questionnaire, administered during a structured interview. The McNemar chi2 test was used to compare the data before and after the diagnosis. A total of 497 persons participated (65.5% males; median age of 40 years; age range, 34-45 years). The most common exposure categories were: heterosexual contact (43.4%), homosexual contact (27.2%), and injecting drug use (20.6%). Although the percentage of drug users significantly decreased after diagnosis, 32.4% of injectors continued to use drugs, and approximately half of them exchanged syringes. Regarding sexual behavior, after diagnosis there was a significant decrease in the number of sexual partners and in stable relationships and an increase in condom use, both for persons with stable partners and those with occasional partners, although the percentage varied according to the specific sexual practice. These results indicate that though at-risk behavior seems to decrease after the diagnosis of HIV infection, seropositive persons continue to engage in at-risk practices, indicating the need for interventions specifically geared toward HIV-positive persons.