This study was designed to evaluate the effect of pulsed signal therapy (PST) on patellofemoral pain syndrome associated with patellar chondropathy. A prospective randomized double‐blind placebo controlled trial included 25 patients (41 knees) between 20 and 50 years with pain due to isolated patellofemoral syndrome with chondropathy. PST group received nine 60‐min daily sessions of PST treatment. Control group received the same protocol of blinded placebo treatment. The main outcome was change from baseline Kujala score at 3 months. After 3 months, patients in the control group received effective treatment (placebo post‐treatment). All patients were then followed, for up to 12 months. Seventeen knees (5 males and 12 females, mean age 36.7 ± 7.9) received placebo and 24 knees (8 males and 16 females, mean age 35.5 ± 8.9) received PST. By the third month, PST group exhibited a mean change from baseline of 9.63 ± 7.5 Kujala points, compared to 0.53 ± 1.8 in the placebo group (P < 0.001). A significant progressive improvement was seen in the PST group between the 3rd and 6th and between the 6th and 12th month (P < 0.016). Patients initially allocated in the control group also improved at 3 months (P < 0.001) and 6 months (P = 0.005) post‐effective treatment. In conclusion, PST in patellofemoral pain syndrome with chondropathy was effective compared to placebo at 3 months, showing an important improvement of Kujala score. The improvement was progressive and maintained up to 12 months. PST is safe and should be considered as a non‐invasive option for management of this condition. Bioelectromagnetics. 40:83–90, 2019. © 2019 Bioelectromagnetics Society