Background: Drug abuse is common all over the world. Abused drugs are psychoactive and make abusers engage into activities which are unacceptable in the community. For injecting drugs, the apparatus used is often shared and is unsterile. Unsterile injecting apparatus predispose the users to blood borne infections. People who use drugs often indulge in unprotected sex which is a risk factor for acquiring sexually transmitted infections. Methods: A cross-sectional study of people who use drugs (PWUDs) aged 18 years and above, was done in Mwanza urban. People who use drugs who were either too sick or unable to answer questions and those who refused to give consent to the study were excluded. Data collection involved use of a questionnaire (Face to face approach) and collection of blood and urine samples. The blood samples were used to determine the serological status of the participants, while the urine samples were used to detect presence of illegal drugs. Complete data was obtained for seven hundred and seventy out of the 774 PWUDs who were initially recruited into the study. Results: The project has shown that cannabis and alcohol are highly abused 83.0% n= 581 and 74.2% n= 519 respectively followed by khat 38.3 % n= 268. Heroin use was recorded in 34.0% n= 238 and heroin injection was noted in 5.6% n= 43 of the illegal drug users. HIV infection was detected in 8.6% of the drug abusers, while hepatitis B was seen in 3.8%, hepatitis C was detected in 2.9% and syphilis was detected in 2.5% of the participants. Conclusion: HIV infection in people who use drugs was high (8.6%) compared to that seen in the general population (5.1%) and also high rates of positive results for hepatitis C and syphilis were recorded. Among the intravenous drug users 6.3% were HIV positive. Recommendations: Education should be given to the substance abusers on the consequences of taking illegal drugs. Safe sex should be advocated, a methadone clinic and sober houses should be established in Mwanza. The Ministry of Home Affairs should increase efforts to prohibit importation of illegal drugs.