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Study Design Randomized controlled trial. Background Evidence suggests that multimodal interventions that include exercise therapy may be effective for patellofemoral pain (PFP); however, no study has investigated the effects of trigger point (TrP) dry needling (DN) in people with PFP. Objectives To compare the effects of adding TrP DN to a manual therapy and exercise program on pain, function, and disability in individuals with PFP. Methods Individuals with PFP (n = 60) recruited from a public hospital in Valencia, Spain were randomly allocated to manual therapy and exercises (n = 30) or manual therapy and exercise plus TrP DN (n = 30). Both groups received the same manual therapy and strengthening exercise program for 3 sessions (once a week for 3 weeks), and 1 group also received TrP DN to active TrPs within the vastus medialis and vastus lateralis muscles. The pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS; 0-100 scale) was used as the primary outcome. Secondary outcomes included other subscales of the KOOS, the Knee Society Score, the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), and the numeric pain-rating scale. Patients were assessed at baseline and at 15-day (posttreatment) and 3-month follow-ups. Analysis was conducted with mixed analyses of covariance, adjusted for baseline scores. Results At 3 months, 58 subjects (97%) completed the follow-up. No significant between-group differences (all, P>.391) were observed for any outcome: KOOS pain subscale mean difference, -2.1 (95% confidence interval [CI]: -4.6, 0.4); IKDC mean difference, 2.3 (95% CI: -0.1, 4.7); knee pain intensity mean difference, 0.3 (95% CI: -0.2, 0.8). Both groups experienced similar moderate-to-large within-group improvements in all outcomes (standardized mean differences of 0.6 to 1.1); however, only the KOOS function in sport and recreation subscale surpassed the prespecified minimum important change. Conclusion The current clinical trial suggests that the inclusion of 3 sessions of TrP DN in a manual therapy and exercise program did not result in improved outcomes for pain and disability in individuals with PFP at 3-month follow-up. Level of Evidence Therapy, level 1b. Prospectively registered July 27, 2015 at www.clinicaltrials.gov (NCT02514005). J Orthop Sports Phys Ther 2017;47(6):392-401. doi:10.2519/jospt.2017.7389.