Objective: Minimizing disability and enhancing physical function to its optimal levels is still a challenge in management of rheumatoid arthritis (RA). The aim is to identify factors leading to disability in RA. Methods: This is a cross-sectional Egyptian multicenter study carried out on 215 RA patients attending to our inpatient and outpatient rheumatology clinics during 4 months starting from April to July 2017 who agreed to participate in the study; 170 patients were from Cairo University hospitals and 45 from Zagazig University hospitals. We recorded a number of possible risk factors including demographic, clinical, serological and therapeutic factors. The assessment of patients’ disability was done using Modified HAQ (MHAQ). Results: A significant positive correlation was found between MHAQ and different markers of activity in addition to age and depression score (P < 0.001). Illiteracy accounted for higher MHAQ scores (P = 0.001). A higher MHAQ was found in patients with ischemic heart disease (P < 0.05). Patients with erosions on X-rays had significantly higher MHAQ scores. Subluxations also accounted for higher MHAQ scores (P = 0.000). Conclusion: Aging, illiteracy, disease activity, erosions, subluxations, depression and ischemic heart disease were all related to higher disability. Good control of disease activity which in turn reduces erosions and subluxations is mandatory. Screening for depression and proper use of anti-depressants is of great value. Proper screening and prophylaxis is recommended against ischemic heart disease by controlling modifiable risk factors like obesity, dyslipidaemia, hypertension, smoking and sedentary lifestyle.