We retrospectively evaluated the effectiveness of prolotherapy in resolving pain, stiffness, and crepitus, and improving physical activity in consecutive chondromalacia patients from February 2008 to September 2009. Sixty-nine knees that received prolotherapy in 61 patients (33 female and 36 male) who were 18-82 years old (average, 47.2 years) were enrolled. Patients received 24 prolotherapy injections (15% dextrose, 0.1% procaine, and 10% sarapin) with a total of 40 cc in the anterior knee. At least 6 weeks after their last prolotherapy session, patients provided self-evaluation of knee pain upon rest, activities of daily living (ADL) and exercise, range of motion (ROM), stiffness, and crepitus. Symptom severity, sustained improvement of symptoms, number of pain pills needed, and patient satisfaction before treatment and improvement after treatment were recorded. Following prolotherapy, patients experienced statistically significant decreases in pain at rest, during ADL, and exercise. Stiffness and crepitus decreased after prolotherapy, and ROM increased. Patients reported improved walking ability and exercise ability after prolotherapy. For daily pain level, ROM, daily stiffness, crepitus, and walking and exercise ability, sustained improvement of over 75% was reported by 85% of patients. Fewer patients required pain medication. No side effects of prolotherapy were noted. The average length of time from last prolotherapy session was 14.7 months (range, 6 months to 8 years). Only 3 of 16 knees were still recommended for surgery after prolotherapy. Prolotherapy ameliorates chondromalacia patella symptoms and improves physical ability. Patients experience long-term improvement without requiring pain medications. Prolotherapy should be considered a first-line, conservative therapy for chondromalacia patella.