Cerebral palsy (CP) is a congenital neurological disorder that causes musculoskeletal weakness and biomechanical dysfunctions. Strength training guidelines recommend at least 70% of 1-repetition maximum to increase muscle strength and mass. However, individuals with CP may not tolerate such high exercise intensity. Blood flow restriction (BFR) can induce similar gains in strength and muscle mass using loads as low as 20% to 30% 1-repetition maximum. This case series described the safety, feasibility, and acceptability of BFR in adults with CP and examined changes in muscle mass and strength. Three male participants with gross motor function classification system level 3 CP underwent strength training using a periodized 8-week BFR protocol. Outcomes included: Safety via blood pressure during and post-BFR exercises in addition to adverse event tracking; Feasibility via number of support people and time-duration of BFR exercises; Acceptability via rate of perceived discomfort (0-10) and qualitative interviews; Muscle Mass via ultrasonographic cross-sectional area of the quadriceps and hamstring; and Strength via (1) 3-repetition maximum in the leg press and knee extension, (2) isometric knee flexor and extensor muscle force measured with a hand-held dynamometer, and (3) 30-second sit-to-stand test. Participants replaced 2 exercises from their current regimen with seated knee extension and leg press exercises using progressively higher limb occlusion pressure and exercise intensity. Limb occlusion pressure started at 60%, by week 4 progressed to 80%, and then remained constant. The exercise repetition scheme progressed from fixed nonfailure repetition sets to failure-based repetition sets. Blood pressure never exceeded safety threshold, and no adverse events were reported. The BFR training was time-consuming and resource-intensive, but well-tolerated by participants (rate of perceived discomfort with a mean value of 5.8, 100% protocol adherence). Strength, as measured by 3-repetition maximum testing and 30-second sit-to-stand test, increased, but isometric muscle force and muscle mass changes were inconsistent. Blood flow restriction may be an effective means to increase strength in adults with CP who cannot tolerate high-intensity resistance training. Future research should compare BFR to traditional strength training and investigate mediators of strength changes in this population. for more insights from the authors (see the Video, Supplemental Digital Content available at: http://links.lww.com/JNPT/A473 ).