Patellofemoral pain syndrome (PFPS) is a commonly diagnosed knee pathology that is twice as prevalent in women. Sports medicine clinicians commonly use exercises to attempt to preferentially activate the vastus medialis oblique (VMO) to enhance medially vectored forces on the patella. Recently, our group confirmed clinical theory that the VMO is neurologically distinct from the vastus medialis (VM). However, the ability to voluntarily activate these muscle sub-sections is still disputed. PURPOSE: To determine how PFPS affects neuromuscular control of VM/VMO and examine if hip rotation during a straight leg raise (SLR) modifies motor patterns. METHODS: Thirteen healthy women and four women with PFPS performed isometric SLR in neutral hip rotation (SLR-NR) and during 30 degrees hip lateral rotation (SLR-LR). Participants performed ramp contractions by tracing a line on a screen with a rate of rise of 7.5% maximal voluntary contraction (MVC) per second up to 75% MVC. Bipolar intramuscular fine-wire electrodes were inserted into the VM and VMO. Initial motor unit firing rates (IFR) and recruitment threshold (RT) forces were measured. Generalized linear mixed models and Tukey post hoc tests were used to assess significant differences. The recruitment thresholds were log-transformed to meet the assumptions of normality of residuals and constant variance within each level. RESULTS: A total of 420 motor units were analyzed. There was a significant interaction effect for Muscle × Group for RT (p=0.02), demonstrating that women with PFPS activated their VMO later (20.4 ± 2.5% MVC) than healthy women (11.2 ± 1.5% MVC; p=0.01). The Group × Hip Position interaction effect was also significant for RT (p=0.02). Healthy women activated their VMO earlier during SLR-NR (9.9 ± 1.5% MVC) than during SLR-LR (14.9 ± 1.5% MVC; p=0.02). Women with PFPS had a delayed VMO onset time (19.1 ± 2.5% MVC) compared to healthy women (9.9 ± 1.5% MVC) in SLR-NR (p=0.02). There was no significant difference in IFR between muscles or hip positions between groups. CONCLUSIONS: Targeted strengthening of the VMO in SLR with a neutral hip rotation is a more effective training position for women with PFPS than using lateral hip rotation.