Background: Recent evidence indicates that combined upper extremity blood flow restriction (BFR, applied distally to the shoulder) and low-load resistance exercise (LIX) augments clinically meaningful responses in shoulder region tissues proximal to the occlusion site. The purpose of this investigation was to determine the efficacy of BFR-LIX for the shoulder when added to standard offseason training in Division IA collegiate baseball pitchers. We hypothesized that BFR-LIX would augment training-induced increases in shoulder-region lean mass, rotator cuff strength, and endurance. As secondary outcomes, we sought to explore the impact of BFR- LIX rotator cuff training on pitching mechanics.Methods: Twenty-eight collegiate baseball pitchers were randomized into 2 groups (BFRN=15 and non-BFR [NOBFR]N=13) that, in conjunction with offseason training, performed 8 weeks of shoulder LIX (Throwing arm only; 2/week, 4 sets [30/15/15/fatigue], 20% isometric max) using 4 exercises (cable external and internal rotation [ER/IR], dumbbell scaption, and side-lying dumbbell ER). The BFR group also trained with an automated tourniquet on the proximal arm (50% occlusion). Regional lean mass (dual-energy x-ray absorptiometry), rotator cuff strength (dynamometry: IR 0 & 90, degrees ER 0 & 90, degrees Scaption, Flexion), and fastball biomechanics were assessed pre and post-training. Achievable workload (sets x reps x resistance) was also recorded. An ANCOVA (covaried on baseline measures) repeated on training timepoint was used to detect within-group and between-group differences in outcome measures (a=0.05). For significant pairwise comparisons, effect size (ES) was calculated using a Cohen's d statistic and interpreted as: 0-0.1, negligible; 0.1-0.3, small; 0.3-0.5, moderate; 0.5-0.7, large; >0.7, and very large (VL). Results: Following training, the BFR group experienced greater increases in shoulder-region lean mass (BFR: T 227 + 60g, NOBFR: T 75 + 37g, P=.018, ES=1.0 VL) and isometric strength for IR 90 degrees (T 2.4 + 2.3 kg, P=.041, ES=0.9VL). The NOBFR group experienced decreased shoulder flexion [ 1.6 + 0.8 kg, P=.007, ES=1.4VL) and IR at 0 degrees [ 2.9 + 1.5 kg, P=.004, ES=1.1VL). The BFR group had a greater increase in achievable workload for the scaption exercise (BFR: T 190 + 3.2 kg, NOBFR: T 90 + 3.3 kg,P=.005, ES=0.8VL). Only the NOBFR group was observed to experience changes in pitching mechanics following training with increased shoulder external rotation at lead foot contact ([ 9.0 degrees +/- 7.9, P=.028, ES=0.8VL) as well as reduced forward 13.6 degrees +/- 2.1, P=.001, ES=1.2VL) and lateral 14.6 degrees +/- 3.4, P=.007, ES=1.0VL) trunk tilt at ball release.Conclusion: BFR-LIX rotator cuff training performed in conjunction with a collegiate offseason program augments increases in shoul- der lean mass as well as muscular endurance while maintaining rotator cuff strength and possibly pitching mechanics in a manner that may contribute to favorable outcomes and injury prevention in baseball pitching athletes.Level of Evidence: Level I; Randomized Controlled Trial; Treatment Study (c) 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.