Background: Patellofemoral pain syndrome (PFPS) is often treated conservatively with voluntary exercise for the Quadriceps femoris. Nevertheless, a substantial percentage of patients remain symptomatic. Although exercise seems a crucial element for treatment, it may serve to increase patellar irritation with the resulting dilemma that patients exercising the muscles may be simultaneously irritating the knee. Patients with PFPS have been using quadriceps strengthening exercises with varying results on muscle strength and pain. However, there are various problems associated with these forms of traditional quadriceps strengthening exercises. This study sought to explore the effects of progressive functional retraining of Vastus Medialis Obliquus (VMO) in the context of PFPS. Purpose: To compare the efficacy of strengthening of VMO Vs Rectus femoris (RF) using open kinematic and closed kinematic chain exercises in PFPS. Methods: This study was conducted at Yenepoya Medical College Hospital, Mangalore. Forty subjects with anterior knee pain fulfilling the inclusion criteria were randomly assigned to two groups with the mean age of 25.85 in group 1 and 27.65 in group 2. Group 1 received RF strengthening exercises. Group 2 received strengthening of VMO. Visual Analog Scale (VAS) and anterior knee Pain Scale were noted before and after the interventions. (i.e. either RF strengthening or strengthening of VMO).Results: After 2weeks of intervention in Group 1 there was a significant increase Anterior knee pain scale(AKPS) with mean difference of 4.95 and VMO co-ordination test status. There was also a significant decrease in the VAS scale and with mean diff of 0.5 , whereas in Group 2, AKPS with mean diff of -23.8 , VAS with the mean diff of 4.5 were all highly significant and there was a increase in VMO co-ordination test but statistically not significant. Conclusion: Strengthening of VMO clinically as well as statistically suggest that strengthening of VMO is more effective than the traditional strengthening of RF in patients with PFPS.