This study examines the outcomes of repeated prostate cancer screening using prostate-specific antigen (PSA) testing and magnetic resonance imaging (MRI) in a population-based, screen-by-invitation randomized clinical trial (STHLM3-MRI). The trial recruited Swedish men aged 50 to 74 years and invited those with PSA levels of 1.5 ng/mL or greater at the first screening to participate in a second screening round 2 to 3 years later. Participants underwent blood sampling for PSA testing and biparametric MRI if their PSA levels were 3 ng/mL or greater. Men with lesions classified as PI-RADS score 3 or greater were referred for targeted and systematic biopsies. The primary outcome was clinically significant prostate cancer (Gleason score ≥3 + 4), while secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score 6), the number of elevated PSA tests, MRI scans, and biopsy procedures. Of the 7609 men invited for the second screening, 2078 (27.3%) were eligible, and 1500 (72.2%) participated. The median age of the participants was 67 years. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater, and 617 underwent MRI, revealing 51 (7.6%) with equivocal lesions and 33 (4.9%) with suspicious lesions. Only 10 of 383 men with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6. The study concluded that while cancer detection during the second screening round was limited, the detection of low-grade cancer remained low, suggesting the need for strategies to reduce MRI-related resource use.This study examines the outcomes of repeated prostate cancer screening using prostate-specific antigen (PSA) testing and magnetic resonance imaging (MRI) in a population-based, screen-by-invitation randomized clinical trial (STHLM3-MRI). The trial recruited Swedish men aged 50 to 74 years and invited those with PSA levels of 1.5 ng/mL or greater at the first screening to participate in a second screening round 2 to 3 years later. Participants underwent blood sampling for PSA testing and biparametric MRI if their PSA levels were 3 ng/mL or greater. Men with lesions classified as PI-RADS score 3 or greater were referred for targeted and systematic biopsies. The primary outcome was clinically significant prostate cancer (Gleason score ≥3 + 4), while secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score 6), the number of elevated PSA tests, MRI scans, and biopsy procedures. Of the 7609 men invited for the second screening, 2078 (27.3%) were eligible, and 1500 (72.2%) participated. The median age of the participants was 67 years. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater, and 617 underwent MRI, revealing 51 (7.6%) with equivocal lesions and 33 (4.9%) with suspicious lesions. Only 10 of 383 men with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6. The study concluded that while cancer detection during the second screening round was limited, the detection of low-grade cancer remained low, suggesting the need for strategies to reduce MRI-related resource use.