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The practice of self-medication is the use of medications without a prescription from a healthcare professional. Globally, rates of self-medication practice range from 32.5% to 81.5%.Thestudy aimed to: Determine the prevalence and factors contributing to self-medication in adults.A cross-sectional study conducted in Serere town focused on the prevalence and factorsinfluencing self-medication in adults. A questionnaire consisting of open-ended and closedendedquestions was administered to respondents to collect data to determine the prevalenceand factors influencing self-medication in adults. The data obtained were coded, edited,entered, summarized, and analyzed using Microsoft Excel 2013. Of the 100 participantssurveyed with a response rate of 100%, the overall prevalence was 89% in number of peopleparticipating in the study. The most common non-prescription drugs used by respondents werePanadol (19.10%), followed by 16.85%, 14.61%, 12.36%, 11.24%, 10.11 %, 8, 99% and 6.74% fordrugs such as Coartem, Vitamin C, Zinc, Azithromycin., Mebendazole, Covidex and Lasixrespectively (Table 2). Factors significantly associated with self-medication are male gender,illiteracy, marital status, chronic disease, low wealth index, unemployment, accessibility topharmacies, and very long distance between home and hospital. Age is an independent factorassociated with self-medication. There was a high rate of self-medication among thosesurveyed. Male gender, illiteracy, marital status, chronic illness, low socioeconomic status,unemployment, accessibility to pharmacies, and very long distance between home and thenearest medical facility are factors significantly associated with self-medication practices. Ageis an independent predictor of self-medication. More studies using larger sample sizes on theprevalence and factors influencing self-medication use among adults in Serere town using largersample sizes should be considered.