Objective: To estimate the prevalence and describe the pattern of OTC use among patients attending primary healthcare (PHC) centers, and to assess their knowledge and attitude regarding the related side effects. Method: A cross-sectional study was carried out among 400 adult patients attending the General Medicine clinic in 10 selected PHC centers in Jeddah, Saudi Arabia. The data collected included socioeconomic parameters, practice and pattern of OTC analgesics use in past 6 months, knowledge and attitude about OTC analgesics, and safety assessment. Results: Results showed that 84.4% of the participants were using OTC analgesics, at least twice per week in 59.3% of the cases, and for <1 week duration in 65.8%. The prevalence of use was highest among illiterate and highly educated participants (p=0.000), and those with moderate income (p=0.011). Acetaminophen (paracetamol) was the most frequently used drug (86.1%), followed by ibuprofen (25.1%) and diclofenac (14.7%); and headache (71.1%), arthralgia (17.7%) and toothache (17.4%) were the most common conditions leading to usage. A simple health problem (64.0%), previous experience with the drug (35.1%) and lack of time (12.1%) were the most common reasons for OTC analgesics use. Among all, 58.1% admitted having no knowledge about OTC analgesic side effects; while 7.1% reported having experienced side effects. Conclusion: There is an alarming prevalence of OTC analgesics use among patients, with inadequate levels of awareness about the associated risks. Awareness and knowledge of users should be further investigated to determine the need for information for this specific or a larger population.Key words: Analgesics, Auto medication, Non-steroid anti-inflammatory, Over-the-counter, Painkiller, Paracetamol. Key MessageThere is high prevalence of OTC analgesics usage combined with low levels of awareness and knowledge about the related hazards; which exposes to misusage that may carry accidents and severe side effects especially among the high-risk populations. The lack of awareness and knowledge highlights the need for targeted information.