Objective: Pharmacists with their unique roles and responsibilities, play a vital role in improving patients knowledge and medication adherence, ultimately contributing to improved health-related quality of life (HRQoL). This study aims to evaluate the impact of pharmacist-led educational intervention on disease knowledge, medication adherence, and HRQoL among patients with rheumatoid arthritis (RA). Methods: A randomized, single-blind, parallel, controlled study was conducted among 118 patients with RA visiting the outpatient department of the National Center for Rheumatic Diseases, Kathmandu, Nepal. Data on disease knowledge, medication adherence, and HRQoL were collected at baseline and follow-up at 12 weeks. Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), General Medication Adherence Scale (GMAS), and European Quality of Life Scale (EuroQol) 5-Dimension 5-Level (EQ-5D-5L) were used to measure knowledge level, adherence level, and HRQoL, respectively. Results: At follow-up, disease knowledge significantly improved in the intervention group (IG) (excellent knowledge: 42;71.2% vs 9;15.3% at baseline), while the change was minimal in control group (CG) (12;20.3% vs 22.0% at baseline). Similarly, the IG showed a marked increase in medication adherence (high: 57;96.6% vs 20;33.9% at baseline), with only slight improvement in CG (37;62.7% vs 29;49.2% at baseline). The Proportion of patients with the best HRQoL significantly increased in the IG (48;81.4% vs 17;28.8% at baseline), while it remained unchanged in CG. Statistically significant improvements were observed in disease knowledge, medication adherence and HRQoL scores (P < .01) in the IG. Conclusion: The intervention group demonstrated significantly improved disease knowledge, medication adherence, and HRQoL scores, while control group showed minimal changes, highlighting the effectiveness of pharmacist-led educational intervention in disease management.