Researchers looked at whether a short (3 weeks) or a long (6 weeks) period of systemic antibiotic treatment is linked with non-inferior clinical remission and adverse events in diabetic foot osteomyelitis (DFO) patients who had surgical debridement (AEs). They randomized (allocation 1:1) patients with DFO after surgical debridement to either a 3-week or 6-week course of antibiotic therapy in this prospective, randomized, non-inferiority pilot study. After the end of therapy, a minimum of 2 months of follow-up was required. The researchers used Cox regression and noninferiority analyses to compare outcomes (25% margin, power 80%). 44 of the 93 enrolled patients (18% females; median age 65 years) were randomly assigned to the 3-week arm and 49 to the 6-week arm out of a total of 93 individuals. The median number of surgical debridements was one (with a range of 0–2). Remission occurred in 37 (84%) of the patients in the 3-week arm compared to 36 (73%) in the 6-week arm in the ITT population (P=.21). The number of adverse events (AEs) in the 2 study arms (17/44 vs. 16/49; P=.51) was comparable, as were the remission rates in the per-protocol (PP) population (33/39 vs. 32/43; P=.26). Treatment with the shorter antibiotic course was not significantly linked with remission in multivariate analysis (ITT population: HR, 1.1 [95% confidence range CI,.6–1.7]; PP population: HR, 0.8 [95% confidence interval CI,.5–1.4]). In a randomized controlled pilot study, a three-week post debridement systemic antibiotic therapy course for DFO produced equivalent (and statistically non-inferior) remission and AE rates to a 6-week regimen.