Difficult-to-treat rheumatoid arthritis (RA) is a significant clinical problem despite no clear definition. We aimed to provide clinical characteristics and associated comorbidities of RA patients in relation to disease control. RA characteristics and physician-recorded comorbidities were analyzed in a sample of 1937 RA patients. Patients treated for RA for 5.2 y (IQR, 2.1-11.3) were classified as difficult-to-control when presenting with DAS28-ESR > 3.2 despite previous use of at least 2 csDMARDs. A comparison of demographic and RA-related characteristics between difficult-to-treat and low disease activity patients (DAS28-ESR ≤ 3.2) was performed. Comorbidity burden was assessed by calculating Rheumatic Diseases Comorbidity Index (RDCI). Logistic regression model was constructed for difficult-to-control disease. Hypertension (46.9% (95%CI, 44.7-49.2)), coronary artery disease (CAD) (18.5% (95%CI, 16.8-20.3)), and diabetes (14.4% (95%CI, 12.9-16.0)) were the most prevalent conditions in RA patients. When compared with the adequate control group, difficult-to-control patients were increasingly burdened with hypertension (52.7% (95%CI, 47.5-57.8) vs. 42.0% (95%CI, 36.6-47.6); p = 0.006), cardiovascular diseases (24.2% (95%CI, 20.1-28.9) vs. 11.1% (95%CI, 8.0-15.1); p < 0.001), respiratory system diseases (7.0% (95%CI, 4.8-10.2) vs. 3.3% (95%CI, 1.8-5.9); p = 0.03) and gastroduodenal ulcers (2.3% (95%CI, 1.2-4.4) vs. 0.3% (95%CI, 0.1-1.8); p = 0.04). Patients with higher RDCI had lower chance to obtain low disease activity (OR 0.69 (95%CI, 0.61-0.79); p < 0.001). In multivariate analysis, RDCI was independently associated with difficult-to-control disease (OR 1.46 (95%CI, 1.21-1.76); p < 0.001). RA patients suffer from a variety of comorbidities. Cardiovascular and respiratory system diseases occur twice as often in difficult-to-control patients. RDCI may provide a valuable tool in evaluating a risk for difficult-to-control RA. Key Points • Hypertension, coronary artery disease and diabetes are the most prevalent comorbidities in rheumatoid arthritis. • Cardiovascular and respiratory tract diseases as well as gastroduodenal ulcers are more common among difficult-to-control patients, when compared with subjects with adequately controlled RA. • Rheumatic Diseases Comorbidity Index is an independent predictor for difficult-to-control RA.