The clinical effects on knee osteoarthritis (OA) symptoms and tissue structure were evaluated after bone marrow-derived mononuclear cell intraarticular injection. A group of 32 patients with 34 knee joints in stage II–III osteoarthritis were treated by intraarticular injection of mononuclear cell suspension. Clinical results were obtained by KOOS (Knee Osteoarthritis Outcome Score) and KSS (Knee Society Score) scores during a 12 months follow-up period. Radiological evaluation was performed using magnetic resonance imaging. A comparison with a control group of 28 patients treated with routinely used three hyaluronic acid intra-articular injections was made. No adverse effects were observed after the bone marrow derived mononuclear cells (BM-MNC) injection. At the end point of the follow up all score results had improved, compared to those at to the starting point. 65% of patients maintained minimal perceptible clinical improvement of the score results. The Whole Organ Magnetic Resonance Imaging Score showed improvement from 44.31 to 42.93 points (p < 0.05) during a 6–7 month period. Comparing score results to the control group, a statistically significant (p < 0.05) improvement in the KOOS pain subscale score at the 6 and 12 months was observed in the mononuclear cell group. BM-MNC injection leads to a decrease of knee OA symptoms and slows changes in structure of the degenerative joint tissue.