Background: Use of potentially inappropriate medication (PIMs) is a prominent concern that leads to significant medication-related issues among older adults. Notably, older women tend to utilize more medicines than men; older women frequently take more drugs. In addition, some evidence suggests that prescription PIMs vary by gender. This study examines the gender-based variation in prescribing PIM among older adults in Saudi Arabia. Methods: A cross-sectional retrospective analysis of electronic medical records from a large hospital in Saudi Arabia was carried out. Patients over the age of 65 who received ambulatory treatment were included in the study. The utilization of PIM was assessed based on Beers criteria. Descriptive statistics and logistic regression were employed to describe patterns of PIM utilization and identify factors associated with their use. All statistical analyses were performed using Version 9.4 of the Statistical Analysis Software (SAS®9.4). Results: The study comprised 4062 older people (age 65) who visited ambulatory care clinics; the average age was (72.6 ± 6.2) years. The majority of the study sample was women (56.8%). Among older adults, 44.7% of older men and 58.3% of older women reported having PIMs that should be avoided, indicating a higher prevalence of PIMs among women compared to men. In terms of the PIM categories used, women had a much higher utilization rate of cardiovascular and gastrointestinal drugs than men. In men, the use of PIMs was frequently associated with hypertension, ischemic heart disease, asthma, osteoarthritis, and cancer, while in women PIM use was associated with age, dyslipidemia, chronic kidney disease, and osteoporosis. Conclusions: This study revealed sex differences in PIM prescribing among older adults; PIM use is more common among women. Sex differences exist in clinical and socioeconomic characteristics and factors related to using potentially inappropriate medications. This study revealed essential areas that could be targeted by further interventions to improve drug-prescribing practices among older adults at risk of PIM.