OBJECTIVE: To compare clinical outcomes in Duchenne muscular dystrophy (DMD) by steroid type within subgroups defined by baseline age, ambulatory function, and steroid duration. BACKGROUND: The standard of care for DMD includes steroids. At the same time, clinical outcomes remain heterogeneous among boys receiving steroid treatment. It is important to understand the extent to which steroid effects might vary across clinically distinct subgroups. DESIGN/METHODS: Placebo arms from four DMD clinical trials with assessments of 48-week change in six-minute walk distance (6MWD) as the primary outcome were studied (NCT01826487, NCT01865084, NCT00592553, NCT01254019). Mean changes in 6MWD and secondary ambulatory outcomes were compared between patients receiving daily deflazacort vs. daily prednisone, adjusting for baseline age, steroid duration, 6MWD, and rise time. RESULTS: A total of n=328 patients were available across placebo arms, with n=231 receiving daily steroids (n=127 deflazacort; n=104 prednisone). Stable steroid use for ?6 months pre-baseline was required in all but one study; all had mean prior steroid use > 1.5 years. Baseline characteristics were balanced across steroid groups. In the overall study population, deflazacort was associated with preservation of 35.4 meters of 6MWD over 48 weeks compared to prednisone (P<0.01). When assessing by subgroups, differences between deflazacort vs. prednisone were most pronounced among boys with the following baseline characteristics: aged ?8 years (+44.5m, P<0.01), rise time ?5 seconds (+41.3m, P<0.01) and steroid duration >3 years (+57.5m, P<0.01). Overall differences between steroid groups in timed function tests and in the linearized North Start Ambulatory Assessment were numerically consistent. CONCLUSION: Benefits of daily deflazacort compared to daily prednisone for preserving ambulatory function in DMD were most evident among patients who were older, had been on steroids longer, or were at a more progressed disease stage. These results add to the evidence for a potential cumulative benefit of deflazacort versus prednisone.