Introduction: Drug incompatibilities are among the most common medication errors in intensive care units. A precipitate can form and block the catheter or cause an adverse event in the patient. Intensive care units have implemented various strategies for limiting the occurrence of these incompatibilities, which have already been studied in vitro under standardized conditions. The objective of the present in vitro study was to continue these assessments by determining the impact of the infusion line geometry and the drugs' position in the infusion set-up on the prevention of vancomycin-piperacillin/tazobactam incompatibility. Methods: Infusion lines with a different common volume, a multilumen medical infusion device, a dilute vancomycin solution, and separate infusions of incompatible drugs were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. Results: Reducing the common volume, using multilumen medical devices, or spacing out the two incompatible drugs on the infusion line did not prevent the occurrence of a significant particulate load. Only dilution of the vancomycin solution was associated with a significantly lower particulate load and the absence of drug incompatibility. Conclusions: Our results show that under specific conditions, it is possible to reduce particulate contamination considerably.