OBJECTIVES A secondary analysis was carried out to test if differences existed in reported treatment satisfaction between non-valvular atrial fibrillation patients (NVAF) treated with vitamin K antagonist (VKA) anticoagulants and new oral anticoagulants (NOAC). METHODS A sample of 1318 patients was recruited at random in the FANTASIIA study, between June 2013 and March 2014, from which 77% were using VKA and 23% NOAC at least 6 months before inclusion. The specific treatment satisfaction instrument SAFUCA was used to test differences between groups. The SAFUCA questionnaire is composed by 7 dimensions and overall score, measured in a 0 (least satisfied), 100 (most satisfied) scale. Guyatt’s d was used to estimate effect size. RESULTS Mean age was 73.8 (SD=9.4) years, and 42.5% were women. Patients using NOACs attained statistically significant higher values in the overall score and in all SAFUCA dimensions. Overall score effect size (NOAC vs VKA) was medium-small (79.91 vs 73.22, d=0.43, p<0.001). Small to large effect sizes were also found by dimension: Effectiveness (77.63 vs 72.70, d=0.33, p<0.01), Ease and Convenience (80.99 vs 73.72, d=0.49, p<0.001), INR Controls (62.35 vs 57.66, d=0.32, p<0.01), Impact on Daily Activities (90.08 vs 81.97, d=0.55, p<0.001), Medication Undesired Effects (86.20 vs 79.21, d=0.47, p<0.001), Satisfaction with Medical Care (80.30 vs 69.38, d=0.74, p<0.001), and Overall Satisfaction (80.30 vs 69.38, d=0.74, p<0.001). CONCLUSIONS SAFUCA questionnaire was able to detect satisfaction differences between NVAF patients treated with NOAC and those treated with VKA, presenting medium effect size in most dimensions. This new evidences offer additional support to the questionnaire validity.