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Patient safety improvement interventions usually address either work systems or team culture. We do not know which is more effective, or whether combining approaches is beneficial.To compare improvement in surgical team performance after interventions addressing teamwork culture, work systems, or both.Suite of 5 identical controlled before–after intervention studies, with preplanned analysis of pooled data for indirect comparisons of strategies.Operating theatres in 5 UK hospitals performing elective orthopedic, plastic, or vascular surgeryAll operating theatres staff, including surgeons, nurses, anaesthetists, and others4-month safety improvement interventions, using teamwork training (TT), systems redesign and standardization (SOP), Lean quality improvement, SOP + TT combination, or Lean + TT combination.Team technical and nontechnical performance and World Health Organization (WHO) checklist compliance, measured for 3 months before and after intervention using validated scales. Pooled data analysis of before—after change in active and control groups, comparing combined versus single and systems versus teamwork interventions, using 2-way ANOVA.We studied 453 operations, (255 intervention, 198 control). TT improved nontechnical skills and WHO compliance (P < 0.001), but not technical performance; systems interventions (Lean & SOP, 2 & 3) improved nontechnical skills and technical performance (P < 0.001) but improved WHO compliance less. Combined interventions (4 & 5) improved all performance measures except WHO time-out attempts, whereas single approaches (1 & 2 & 3) improved WHO compliance less (P < 0.001) and failed to improve technical performance.Safety interventions combining teamwork training and systems rationalization are more effective than those adopting either approach alone. This has important implications for safety improvement strategies in hospitals.