BackgroundCorticosteroid injections and aspirations are common interventions for managing musculoskeletal and inflammatory conditions. However, there remains limited safety evidence to support injection decisions and peri‐procedural management in people on anti‐thrombotics, particularly for direct oral anticoagulants (DOACs).ObjectivesTo investigate peri‐procedural management and bleeding complications following musculoskeletal injections or aspirations with anti‐thrombotic medication use.DesignA prospective observational study was undertaken (October 2018–December 2020) in Orthopaedics, Rheumatology and Radiology specialities in two large UK healthcare providers. Data collection involved weekly identification of musculoskeletal procedures, emergency attendance or admission within 30 days and follow‐up questionnaires sent within 2 weeks post‐procedure. Descriptive statistics were used to analyse anticoagulant/anti‐platelet use, peri‐procedural management and bleeding complications.ResultsOf 5080 procedures, 237 of 1338 responses reported antithrombotic use: warfarin (n = 36), DOACs (n = 75) and antiplatelets (n = 126). There were no self‐report or electronic identification of clinically significant bleeding events/complications. Only local bruising was reported (8.6% vs. 0.2% with non‐use), and only with medication continuation or international normalised ratio (INR) levels ≥3.8 or unknown. Only 3/72 DOAC use was interrupted.ConclusionsIn this study, no clinically significant bleeding events or complications were reported or identified following musculoskeletal injections or aspirations, with only localised bruising reported. It was not universal practice to check INR levels and DOAC interruption was uncommon. Findings add evidence that musculoskeletal procedures appear to be low risk procedures for bleeding complications with antithrombotic continuation and when INR levels within lower target range. Research on intra‐articular or soft tissue iatrogenic consequences would add to risk/benefit evaluations.