While povidone-iodine (5% aqueous) preparations have historically been considered the most effective antimicrobial prophylaxis for ophthalmic procedures and have been adopted as routine for intravitreal injections, post-procedure pain is a commonly recognized adverse event of IVI and has typically been attributed to chemical sensitivity (not allergy) to povidone-iodine on the ocular surface. In this paper the authors describe their experience with 0.1% chlorhexidine gluconate. After instilling a drop of topical anaesthesia (tetracaine), an initial drop of 0.1% chlorhexidine gluconate was instilled prior to lignocaine gel anaesthesia and the eye taped closed (10 mins). Following adequate anaesthesia time, the eye was irrigated with 0.1% chlorhexidine gluconate and a surgical drape applied. A further drop of chlorhexidine was instilled over the area marked for injection immediately prior to the injection. They reported an endophthalmitis rate of 0.023% in the 4322 cases performed which was comparable with the published rates of endophthalmitis with povidone-iodine preparations. They also reported a decrease in the patient reported average pain score from eight of 10 to three of 10. Chlorhexidine gluconate could be considered as an alternative to povidone-iodine in patients receiving intravitreal injections, especially those with prior adverse reactions, however care should be taken to ensure that adequate time is allowed (10 minutes vs. two minutes for povidone-iodine).