Background: We implemented a blood flow restriction resistance training (BFR-RT) intervention during an 8-week rehabilitation programme in anterior cruciate ligament reconstruction (ACLR) patients within a National Health Service setting. Objective: To compare the effectiveness of BFR-RT and standard-care traditional heavy-load resistance training (HL-RT) at improving skeletal muscle hypertrophy and strength, physical function, pain and effusion in ACLR patients following surgery. Methods: 28 patients scheduled for unilateral ACLR surgery with hamstring autograft were recruited for this parallel-group, two-arm, single-assessor blinded, randomised clinical trial following appropriate power analysis. Following surgery, a criteria-driven approach to rehabilitation was utilised and participants were block randomised to either HL-RT at 70% repetition maximum (1RM) (n = 14) or BFR-RT (n = 14) at 30% 1RM. Participants completed 8 weeks of biweekly unilateral leg press training on both limbs, totalling 16 sessions, alongside standard hospital rehabilitation. Resistance exercise protocols were designed consistent with standard recommended protocols for each type of exercise. Scaled maximal isotonic strength (10RM), muscle morphology of the vastus lateralis of the injured limb, self-reported function, Y-balance test performance and knee joint pain, effusion and range of motion (ROM) were assessed at pre-surgery, post-surgery, mid-training and post-training. Knee joint laxity and scaled maximal isokinetic knee extension and flexion strength at 60°/s, 150°/s and 300°/s were measured at pre-surgery and post-training. Results: Four participants were lost, with 24 participants completing the study (12 per group). There were no adverse events or differences between groups for any baseline anthropometric variable or pre- to post-surgery change in any outcome measure. Scaled 10RM strength significantly increased in the injured limb (104 ± 30% and 106 ± 43%) and non-injured limb (33 ± 13% and 39 ± 17%) with BFR-RT and HL-RT, respectively, with no group differences. Significant increases in knee extension and flexion peak torque were observed at all speeds in the non-injured limb with no group differences. Significantly greater attenuation of knee extensor peak torque loss at 150°/s and 300°/s and knee flexor torque loss at all speeds was observed with BFR-RT. No group differences in knee extensor peak torque loss were found at 60°/s. Significant and comparable increases in muscle thickness (5.8 ± 0.2% and 6.7 ± 0.3%) and pennation angle (4.1 ± 0.3% and 3.4 ± 0.1%) were observed with BFR-RT and HL-RT, respectively, with no group differences. No significant changes in fascicle length were observed. Significantly greater and clinically important increases in several measures of self-reported function (50–218 ± 48% vs. 35–152 ± 56%), Y-balance performance (18–59 ± 22% vs. 18–33 ± 19%), ROM (78 ± 22% vs. 48 ± 13%) and reductions in knee joint pain (67 ± 15% vs. 39 ± 12%) and effusion (6 ± 2% vs. 2 ± 2%) were observed with BFR-RT compared to HL-RT, respectively. Conclusion: BFR-RT can improve skeletal muscle hypertrophy and strength to a similar extent to HL-RT with a greater reduction in knee joint pain and effusion, leading to greater overall improvements in physical function. Therefore, BFR-RT may be more appropriate for early rehabilitation in ACLR patient populations within the National Health Service.