Purpose The aim of this study was to compare the perioperative time and economic impact of a licensed intracameral anaesthetic/mydriatic combination (Mydrane) during routine cataract surgery. Methods A real-life, prospective, comparative study was performed in 3 clinical centres in France. Preoperative, surgical, and post-operative times were determined for two mydriasis strategies using conventional preoperative mydriatics/anaesthetics eye drops (control regimen) or Mydrane administered at time of surgery. Staff, surgery schedules and drugs utilisation were collected over 12 surgery half-days. The total cost of each strategy was estimated based on treatment cost and nursing costs. Results The analysis included 112 routine cataract surgeries (57 surgeries using Mydrane and 55 using the topical regimen) without protocol deviations or complicated surgery. Overall, the mean time between administration of the first mydriatic eye drops or Mydrane and the end of the surgery was 27.4 ± 21.1 min in the Mydrane group vs. 90.3 ± 30.4 min in the control group (P < 0.0001). The total time of the procedure (from admission to discharge) was not significantly different between groups (P = 0.1611). On average, the extra cost of drugs per patient in the Mydrane group (€5.81) was almost balanced by the reduced nursing time (€5.57) with some variations between centres, due to different organisation including staff resource and consumable. Conclusions The Mydrane strategy produced perioperative nursing time saving and cost reduction provided that adaptation and reorganisation of routine cataract surgery are implemented.