The purpose of this research article is to evaluate the efficacy and the safety of injections of stromal vascular fraction (SVF), obtained with mini-lipoaspiration of fat tissue for knee osteoarthritis and cartilage lesions. Between January 2018 and February 2021, a total of 76 patients (45 females and 31 males, mean age 64 years; range 53-75 years, body mass index [BMI] no more than 30%, with symptomatic primary osteoarthritis of the knee, without previous arthroscopic intervention) underwent a local tumescent lipoaspiration procedure of 60-80cc of fat tissue from the abdomen. SVF was obtained after centrifugation according to the AdiPrep® Adipose Transfer System (Harvest-Terumo, Plymouth, Massachusetts) technique. The final product was checked with flow cytometry for absolute numbers, vitality, and the cluster of differentiation (CD) population. It was injected intraarticularly into the patients knees. Patients were divided in two groups: Group 1 had patients with knee osteoarthritis Kellgren-Lawrence grade early 4 and Group 2 with osteoarthritis K-L grade 2-3. The International Knee Documentation Committee (IKCD) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaires were used to evaluate clinical effects and measure patient's subjective assessment of pain, joint mobility, and physical disability before the injections. They were repeated at six months, one year, two years, and three years post injections. Knee cartilage lesions patients were divided in two subgroups: Group A (11 patients with OA K-L grade 2-3 and Outerbridge cartilage lesions grade 2-3) and Group B (7 patients with OA K-L grade early 4 and cartilage lesions Outerbridge grade late 3 to early 4) were estimated with quantitive analysis of magnetic resonance imaging (MRI) at one, two, and three years post injections. The average IKDC score in Group 1 was 45.9, 63.2, 62.4, 60, and 52. The KOOS score of the same group was 53, 79, 72, 69, and 62 at the end of the third year. At baseline, the average total IKDC score in Group 2 was 48.3, at 6 months 78.2, at one year 77, at two years 70.4, and at three years 61. The KOOS score of this group was 57, 84, 86, 79, and 69 at three years, respectively. For the patients with cartilage lesions, Group A presented lesser volume mean numbers of the lesion: 74% at the end of the first year post injection, 61% at the second, and 52% at the end of the third year with two out of seven patients in the group. The rest had no significant difference. Lesser volume mean number of the lesions in Group B was 85-88%, 70%, and 61% at the end of the third year in 5 out of 11 patients in the group. The rest had no significant difference. Adipose-derivedSVF, injected intraarticularly in arthritic knees, seems to provide good to excellent clinical results for three years and radiological results for cartilage lesions for two years post injections. All patients were satisfied with this treatment with reduction in pain and better joint mobility, especially after two to three months and up to three years. No serious side effects or complications were reported.