Objective To study the prevalence of suprapatellar fat pad (SPFP) MR alterations in asymptomatic subjects, in relation to a wide range of clinical/imaging parameters, including muscle performance tests and physical activity data. Materials and methods We prospectively included 110 asymptomatic subjects as part of a cohort study. Inclusion criteria were no knee pain in the last year. Exclusion criteria were any medical/surgical history of a knee disorder. Subjects underwent knee and low-dose posture radiographs [EOS®], 3 T MRI, clinical examination including muscle performance tests, and physical activity monitoring. The presence/absence of SPFP alterations (hyperintensity and mass effect) were assessed through consensus reading on fluid-sensitive sequences. Differences between groups of knees with SPFP alterations and controls were tested for a total of 55 categorical/continuous clinical/imaging parameters, including SPFP relative-T2-signal, trochlear/patellar/lower-limb morphologic measurements. Wilcoxon-rank-sum and chi-square tests were used to compare groups of patients. The histological correlation was obtained in a cadaveric specimen. Results SPFP alterations were common in asymptomatic subjects: hyperintensity 57% (63/110) and mass effect 37% (41/110), with 27% (30/110) showing both. Among the 55 imaging, clinical, or activity parameters tested, only increased patellar tilt angle (p = 0.02) and TT-TG distance (p = 0.03) were statistically different between groups of SPFP alterations and controls. The histological correlation showed more abundant connective tissue in SPFP compared to the prefemoral fat pad. Conclusions SPFP hyperintensity and mass effect are common MRI findings in asymptomatic knees, and they are not related to most imaging, clinical, and activity parameters. Care should be taken not to overcall them pathological findings as they most likely represent normal variants.