Objectives: The aim of this study was to measure the frequency of medication adherence in rheumatoid arthritis (RA) patients and to assess factors affecting it, deal with some factors to improve adherence and reevaluate after six months. Methods: A prospective cohort interventional study of 100 patients with RA under treatment fulfilled the American College of Rheumatology / European League against Rheumatism (ACR/EULAR) criteria. All patients subjected to full history taking including socio-demographic data, medication and clinical examination, Assessment of disease activity by DAS28, functional ability by Health Assessment Questionnaire (HAQ) score, pain by Visual Analogue Scale (VAS) scale, adherence to treatment by Compliance Questionnaire of Rheumatology (CQR) and Power Doppler U/S for both metacarophalangeal and wrist joints were done at baseline and after 6 months at the end of the study. Analysis of factors of non-adherence was done at baseline before intervention. Results: The baseline adherence rate (CQR≥80) was 37%. The cost of medication (62%), non-availability of medication in pharmacy (59%), lack of belief in the benefit of treatment (38%) forgetting the medication (37%) ,poor provider-patient relationship (25%), inadequate follow up (23%) and polypharmacy (20%) were the most common causes of non adherence in non adherent patients (p˂ 0.05). Adherent patients to drug treatment were younger, living inside Cairo, with higher level of education and nonsmoker. Non-adherent patients had longer morning stiffness duration (p=0.013), more tender joints, higher DAS28 and HAQ scores, higher ESR and CRP titer (p<0.001) and higher frequency of active synovitis in Doppler ultrasound. They also had significantly more frequency of having medications on their expense (p<0.001). After 6 months of follow up and trying to correct the causes of non-adherence, the adherence rate increased to 69% and this associated with improvement in disease activity, functional state and ultrasongraphic findings. Conclusion: Adherence rate to drug treatment in RA patients at baseline was low (37%). It was associated with higher disease activity, functional disability. Patient education, financial support, good physician-patient relationship and simplification of the prescription were found to improve the patient adherence to treatment and to control disease activity after follow up. [Egypt J Rheumatology & Clinical Immunology, 2016; 4(1): 81-92]