A secondary analysis of the STHLM3-MRI randomized clinical trial evaluated outcomes of repeated prostate cancer screening using PSA testing and MRI. Among 7609 men initially screened, 2078 (27.3%) were eligible for rescreening, with 1500 (72.2%) participating. Their median age was 67 years. Of those, 667 had PSA levels of 3 ng/mL or greater, with 617 undergoing MRI. MRI findings showed 51 (7.6%) with equivocal lesions (PI-RADS score 3) and 33 (4.9%) with suspicious lesions (PI-RADS score ≥4). Only 10 of 667 men with prior negative MRI results had lesions with PI-RADS score 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had clinically significant cancer (Gleason score ≥3+4), including 19 (1.3%) with a score of 4+3 or greater and 11 (0.7%) with a score of 6. The detection of low-grade cancer remained low, and a high proportion of MRI scans lacked suspicious lesions. The study suggests that strategies to reduce MRI-related resource use are needed. The detection of clinically significant cancer was limited, and the long-term detection rate remains to be shown. The findings indicate that repeated screening with PSA and MRI has limited effectiveness in detecting clinically significant cancer, but a nonnegligible detection rate was observed. The study highlights the need for improved risk stratification and personalized screening intervals.A secondary analysis of the STHLM3-MRI randomized clinical trial evaluated outcomes of repeated prostate cancer screening using PSA testing and MRI. Among 7609 men initially screened, 2078 (27.3%) were eligible for rescreening, with 1500 (72.2%) participating. Their median age was 67 years. Of those, 667 had PSA levels of 3 ng/mL or greater, with 617 undergoing MRI. MRI findings showed 51 (7.6%) with equivocal lesions (PI-RADS score 3) and 33 (4.9%) with suspicious lesions (PI-RADS score ≥4). Only 10 of 667 men with prior negative MRI results had lesions with PI-RADS score 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had clinically significant cancer (Gleason score ≥3+4), including 19 (1.3%) with a score of 4+3 or greater and 11 (0.7%) with a score of 6. The detection of low-grade cancer remained low, and a high proportion of MRI scans lacked suspicious lesions. The study suggests that strategies to reduce MRI-related resource use are needed. The detection of clinically significant cancer was limited, and the long-term detection rate remains to be shown. The findings indicate that repeated screening with PSA and MRI has limited effectiveness in detecting clinically significant cancer, but a nonnegligible detection rate was observed. The study highlights the need for improved risk stratification and personalized screening intervals.