OBJECTIVES: To measure over-the-counter (OTC) drug misuse in the elderly and study its relationship with health-related quality of life (HRQOL). In addition, adverse drug events (ADEs) due to OTC misuse and its relationship to HRQOL were examined. METHODS: A questionnaire will be administered to a sample of elderly patients, aged 65 and above, selected randomly from those attending community wellness programs in the Houston area. Information on OTC drug use/misuse, ADEs, HRQOL and demographic data were obtained using a combination of self-administered questionnaire and personal interview technique. HRQOL was measured using the SF-12v2 scale and analyzed using the SAS statistical package at a priori set significance level of 0.05. RESULTS: A total of 157 surveys were collected resulting in a correct response rate of 66.53% from four senior retirement centers. There were slightly more males (56.21%) and Hispanic participants (67.55%) with a median age of 74 years. Misuse occurred in 18% of the respondents and ADEs in 23%. The mean physical (PCS) and mental (MCS) component scores of the SF-12 scale were similar for the elderly (PCS = 52. 53 ± 8.35, MCS = 53.99 ± 6.91). There was no significant difference in the occurrence of ADEs between those who did or did not misuse OTC products. Although there was no significant difference in HRQOL in those who did or did not misuse OTC products, there was a significant difference in HRQOL between those who experienced ADEs (PCS = 49.50 ± 6.86) and those who did not (PCS 53.49 ± 8.21). However, the significant effect was predominately associated with the PCS and its domains namely, physical functioning, role physical, and general health. CONCLUSIONS: Understanding trends in OTC drug use and misuse will help in devising methods to prevent ADEs and additionally improve HRQOL.