The objective was to compare the efficacy and safety of intramuscular methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in the treatment of polymyalgia rheumatica (PMR), a common steroid-treated illness where prolonged therapy can lead to steroid side-effects. The cumulative dose with i.m. MP injections given every 3-4 weeks is considerably smaller than that with conventional OP, and may therefore be associated with fewer long-term side-effects. A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks. The study was multicentre hospital out-patient based and included 60 patients with untreated PMR. In the double-blind phase, either 120 mg 3-weekly i.m. MP or gradually tapering daily OP (initial dose 15 mg) were administered. In the open phase, subjects continued their active treatment with gradual tapering of the steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of disease activity, i.e. sedimentation rate, pain and morning stiffness, and percentage of adverse reactions and serious complications such as fractures, were the main outcome measures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25 OP:24 i.m. MP) completed the study. There were similar remission rates after the double-blind phase (60.6% OP and 66.6% i.m. MP, respectively) and similar disease control in the succeeding open phase. With steroid tapering, the mean erythrocyte sedimentation rate for the entire cohort registered a significant increase in the absence of an increase in symptoms. At 96 weeks, the cumulative mean steroid dose in subjects treated with i.m. MP was equivalent to 56% that of subjects treated with OP. There were eight fractures with OP compared to one on i.m. MP. Mean weight gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg, P < 0.005). Minor adverse reactions were similar in both groups apart from slightly increased bruising with i.m. MP. Only patients on OP reported moon face, hypertension, cataracts, back pain and depression, but the numbers were small. It is possible to achieve equivalent long-term disease control in PMR with i.m. MP compared to OP. I.m. MP was associated with far fewer fractures and lesser weight gain, presumably related to lower cumulative dose. These findings may have implications in the steroid treatment of PMR, and other rheumatic and non-rheumatic diseases.