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Supplemental digital content is available in the text. Purpose: To investigate the effects of blood flow–restricted resistance exercise (BFRRE) on myofiber areas (MFA), number of myonuclei and satellite cells (SC), muscle size and strength in powerlifters. Methods: Seventeen national level powerlifters (25 ± 6 yr [mean ± SD], 15 men) were randomly assigned to either a BFRRE group (n = 9) performing two blocks (weeks 1 and 3) of five BFRRE front squat sessions within a 6.5-wk training period, or a conventional training group (Con; n = 8) performing front squats at 60%–85% of one-repetition maximum (1RM). The BFRRE consisted of four sets (first and last set to voluntary failure) at ~30% of 1RM. Muscle biopsies were obtained from m. vastus lateralis (VL) and analyzed for MFA, myonuclei, SC and capillaries. Cross-sectional areas (CSA) of VL and m. rectus femoris were measured by ultrasonography. Strength was evaluated by maximal voluntary isokinetic torque (MVIT) in knee extension and 1RM in front squat. Results: BFRRE induced selective increases in type I MFA (BFRRE: 12% vs Con: 0%, P < 0.01) and myonuclear number (BFRRE: 18% vs Con: 0%, P = 0.02). Type II MFA was unaltered in both groups. BFRRE induced greater changes in VL CSA (7.7% vs 0.5%, P = 0.04), which correlated with the increases in MFA of type I fibers (r = 0.81, P = 0.02). No group differences were observed in SC and strength changes, although MVIT increased with BFRRE (P = 0.04), whereas 1RM increased in Con (P = 0.02). Conclusions: Two blocks of low-load BFRRE in the front squat exercise resulted in increased quadriceps CSA associated with preferential hypertrophy and myonuclear addition in type 1 fibers of national level powerlifters. [ABSTRACT FROM AUTHOR]