Purpose <p>Medication-related quality of life (MRQoL) is a major subset of quality of life. No studies have examined MRQoL in patients using Saudi Arabia’s advanced electronic service “Wasfaty” to prescribe medications online. Hence, this study assessed MRQoL in service users.</p> Methods <p>A cross-sectional study was conducted between April and October 2024 in primary healthcare centers administered by the Ministry of Interior in the Eastern Province, Saudi Arabia. Patients who utilized the electronic service within 12 months were eligible to participate in the study. Based on several developed versions of the MRQoL scale, the current study established a modified version to mainly cover and measure aspects related to the implemented advanced electronic service. The score ranges between 0 and 100, with higher scores indicating better MRQoL.</p> Results <p>A total of 272 adults participated in the study with an overall MRQoL median score of 76.47. There was no significant impact of age (<i>p</i> = 0.808), sex (<i>p</i> = 0.992), chronic disease status (<i>p</i> = 0.136), and utilization of the advanced electronic service (<i>p</i> = 0.453) variables on the MRQoL. However, polypharmacy was a significant factor that affected MRQoL, particularly the aspect of the practice in obtaining and using medications (<i>p</i> = 0.029).</p> Conclusion <p>The current study showed that the MRQoL among patients utilizing the electronic service to receive their medications in Saudi Arabia was relatively moderate. Lower MRQoL scores were obviously observed in domains related to medication use and side effects. These findings suggest that official practice should include a thorough drug review to improve patient MRQoL.</p>