Purpose <p>To investigate health-related quality of life (HRQoL) after atrial fibrillation (AF) detected by screening compared with conventional AF diagnosis.</p> Methods <p>We used HRQoL data (EQ-5D-5L) from 6004 persons randomised to AF screening with implantable loop recorder and treatment (<i>n</i> = 1501) or to usual care (<i>n</i> = 4503). Annual assessments yielded individual EQ-5D-5L-index (worst=-0.76 best = 1.00) and EQ-VAS scores (Visual Analogue Scale, 0 = worst, 100 = best). Changes were estimated with linear mixed models from before to after incident AF, stroke, and major bleeding. Interaction analyses assessed differences between the randomisation groups.</p> Results <p>During three years of follow-up, 693 of 6004 (12%) participants were diagnosed with AF (Screening: 424 of 1501 (28%), usual care: 269 of 4503 (6.0%)), with 636 alive at year three. For participants developing AF, the EQ-5D-5L index score in the screening group declined from 0.87 before to 0.85 after AF (<i>p</i> &lt; 0.001), and from 0.83 before to 0.79 after AF (<i>p</i> &lt; 0.001) in usual care, with less HRQoL decline in the screening group (<i>p</i> = 0.019). For patients developing stroke and major bleeding, the EQ-5D-5L index scores in the screening group declined from 0.82 to 0.78 (<i>p</i> &lt; 0.001) and 0.82 to 0.76 (<i>p</i> &lt; 0.001) before and after diagnosis, and from 0.84 to 0.76 (<i>p</i> &lt; 0.001) and 0.85 to 0.76 (<i>p</i> &lt; 0.001) in usual care, without differences between the randomisation groups. All EQ-VAS analyses yielded very similar results.</p> Conclusion <p>AF detected through screening had little negative impact on HRQoL compared with AF detected by usual care. Stroke and major bleeding were followed by large HRQoL reductions, regardless of randomisation group.</p> Trial registration <p>The LOOP study is registered at ClinicalTrials.gov, identifier: NCT02036450.</p> Graphical Abstract <p></p>