One hundred and forty-five patients with knee osteoarthritis were randomized in this non-inferiority trial to receive an intramuscular glucocorticoid injection (n=74) or an intra-articular glucocorticoid injection (n=71). The primary outcome of interest was pain at 4 weeks as measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain sub-scale. Secondary outcomes included KOOS pain scores at the remaining time-points, as well as KOOS symptom score, KOOS function score, KOOS sport & recreation score, KOOS quality of life score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and total scores, pain on a Numeric Rating Scale (NRS) and osteoarthritis pain scale, the EuroQol 5 dimensions 5-responses (EQ-5D) quality of life questionnaire, perceived recovery, and adverse events. Outcomes were assessed up to 24 weeks post-treatment. Non-inferiority in the intramuscular group was not established for KOOS pain scores at 4 weeks, but was found to be non-inferior to intra-articular injections at 8 and 24 weeks. No significant differences in any secondary outcomes were recorded.