Introduction: Osteoarthritis (OA) is a degenerative joint disease that affects undreds of millions worldwide, mainly the elderly. The management of OA included a combination of non-pharmacological interventions and pharmacologic agents. Symptomatic slow-acting drugs for OA, particularly glucosamine plus chondroitin sulfate (GS/CS), are effective for symptom relief, protect joint cartilage and delay OA progression, with a good safety profile. Abexol, a mixture of beeswax alcohols that inhibits both cyclooxygenase and 5-lipoxygenase activities, has been effective in experimental and clinical OA studies, showing also a chondroprotective effect. Objective: To compare the effects of Abexol and GS/SC administered for 24 weeks on patients with OA symptoms. Methods: Patients were randomized to Abexol (50 mg) or GS/CS (375/300 mg) once daily for 24 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the visual analogy scale (VAS) scores. The primary outcome was the reduction of the total WOMAC score. Secondary outcomes included WOMAC pain, stiffness and function scores, VAS score and rescue medication consumption. Results: Of 60 randomized patients, 55 completed the study. Abexol and GS/SC reduced significantly total WOMAC score (71 % and 74 %, respectively), and pain, joint stiffness and physical function scores versus placebo. VAS scores decreased significantly with Abexol (66.4 %) and GS/SC (71.2 %). The reductions, significant from the six week, were enhanced over the trial. Rescue medications were consumed by 18/30 Abexol and 16/30 GS/SC patients. No differences between groups were found. Treatments were well tolerated. Conclusions: Abexol and GS/SC administered for 24 weeks improved OA symptoms in patients with diagnostic osteoarthritis and both treatments shown comparable efficacy and safety.