Introduction:To compare the efficacy, safety, and tolerability of transdermal patches of diclofenac sodium with oral diclofenac sustained release (SR) in patients of chronic musculoskeletal MSK pain conditions.Materials and Methods:The eligible patients were given either transdermal diclofenac patch or tablet diclofenac SR. Pain was assessed at 2 and 4 weeks using a visual analog scale. Adverse events were recorded. Patients with 18–65 years old of either gender with score of ≥4 on a 11-item numeric rating scale-numeric version of visual analog scale for pain with diagnosis of primary osteoarthritis (OA) of the knee or hand of at least 3 months duration, with independent radiological confirmation of OA or having pain associated with other MSK conditions such as soft-tissue rheumatism, cervical and lumbar back pain, and fibromyalgia, of at least 3 months duration were included in this study.Results:Transdermal diclofenac diethylamine patch and tablet diclofenac sodium sustained release (SR) do not significantly differ in the reduction of numerical rating scores at the end of 4 weeks (P = 0.8393).Conclusion:Transdermal diclofenac was equi-efficacious as tablet diclofenac sodium SR in reducing pain due to chronic MSK pain conditions.