Background Quadriceps strengthening exercises are part of the treatment of patellofemoral pain (PFP), but the heavy resistance exercises may aggravate knee pain. Blood flow restriction (BFR) training may provide a low-load quadriceps strengthening method to treat PFP. Methods Seventy-nine participants were randomly allocated to a standardised quadriceps strengthening (standard) or low-load BFR. Both groups performed 8 weeks of leg press and leg extension, the standard group at 70% of 1 repetition maximum (1RM) and the BFR group at 30% of 1RM. Interventions were compared using repeated-measures analysis of variance for Kujala Patellofemoral Score, Visual Analogue Scale for ‘worst pain’ and ‘pain with daily activity’, isometric knee extensor torque (Newton metre) and quadriceps muscle thickness (cm). Subgroup analyses were performed on those participants with painful resisted knee extension at 60°. Results Sixty-nine participants (87%) completed the study (standard, n=34; BFR, n=35). The BFR group had a 93% greater reduction in pain with activities of daily living (p=0.02) than the standard group. Participants with painful resisted knee extension (n=39) had greater increases in knee extensor torque with BFR than standard (p<0.01). No between-group differences were found for change in Kujala Patellofemoral Score (p=0.31), worst pain (p=0.24), knee extensor torque (p=0.07) or quadriceps thickness (p=0.2). No difference was found between interventions at 6 months. Conclusion Compared with standard quadriceps strengthening, low load with BFR produced greater reduction in pain with daily living at 8 weeks in people with PFP. Improvements were similar between groups in worst pain and Kujala score. The subgroup with painful resisted knee extension had larger improvements in quadriceps strength from BFR. Trial registration number 12614001164684.