Twelve randomized controlled trials including 1,125 patients with knee osteoarthritis were included in this systematic review, with 11 studies (n = 1,005) analyzed in the meta-analysis comparing low (<40 mg), usual (40 mg), and high (>40 mg methylprednisolone-equivalent) intra-articular corticosteroid injections versus normal saline. Outcomes of interest were pain reduction at very short term (1–3 weeks), short term (4–8 weeks), and middle term (10–16 weeks), along with adverse effects. Low doses significantly improved pain versus saline in the very short term, usual doses were superior in the short term, and high doses were superior in the middle term. Dose significantly influenced pain reduction in the short and middle term but not in the very short term. Findings suggest higher doses may prolong pain relief without increasing serious adverse effects.