Introduction: An intracameral mydriatic and anaesthetic combination has been approved for injection into the anterior chamber in order to provide rapid and stable mydriasis and sustained intraocular anaesthesia during cataract surgery. Methods: In this prospective study, conducted at the Eye Clinic, University of Florence, Italy, we compared phacoemulsification using the standard mydriatic-anaesthetic eye-drop protocol with that using the standard protocol in terms of corneal changes, ocular surface parameters and visual quality. Sixty patients (60 eyes) were included in the study, with 30 eyes receiving MydraneÒ, a novel injectable intracameral solution, during phacoemulsification (Mydrane protocol, MP) and 30 eyes receiving the standard mydriatic-anaesthetic eye drops (standard protocol, SP). The following parameters were assessed using in vivo confocal microscopy (IVCM): central corneal thickness (CCT); flare and cells in the aqueous humor (Flare); keratocyte activation (KA), Langerhans' cell density (LCD), nerve fibre density (NFD) and endothelial cell density (ECD). The Ocular Surface Disease Index (OSDI) score, tear breakup time (TBUT) and Schirmer's test I (STI) were also evaluated. The Optical Scattering Index (OSI) and its standard deviation (OSI-SD) were assessed using the Optical Quality Analysing System (Visiometrics SL, Terrassa, Spain). Results: In the MP group, CCT, Flare, KA and LCD values returned to baseline values within 15 postoperative days. The mean ECD and NFD decreased significantly in both groups from baseline at all follow-up assessments, with no statistically significant difference between groups. TBUT returned to the preoperative level at postoperative day 15 in the MP group. OSDI scores and STI were significantly worse in both groups at all follow-up assessments compared to baseline. At postoperative day 15 OSI and OSI-SD values were significantly better in the MP group than in the SP group. Conclusions: The use of Mydrane during cataract surgery showed a good safety profile and few toxic side effects, ensuring better optical quality and tear film stability.