Retinal microvascular calibre has been proposed as a predictor of cardiac events. Surgery is a major stimulus for inflammation which potentially affects small vessel calibre. This study examined the effects of surgery on retinal, and thus systemic, small vessel size, and the potentially confounding effect of surgery when retinal vessel calibre is used to predict cardiac risk in hospital patients. Consecutive participants were recruited from a preoperative assessment clinic at a teaching hospital. They provided demographic and clinical details, and underwent retinal imaging before and again, within 3 days after surgery, with a non-mydriatic retinal camera. Images were graded for vessel calibre using semi-automated software based on the Parr-Hubbard formula with Knudtson’s modification (IVAN, U Wisconsin). Differences were examined using Fisher’s exact test or a paired t-test, and calibre determinants identified from univariate and multiple linear regression analysis (STATA version 11.2). Sixty-eight participants (23 men, 34%) with a mean age of 55 ± 14.5 years, were recruited. Fourteen (21%) underwent a laparotomy which was considered major surgery and 54 (79%) had Other surgery. Mean C-reactive protein (CRP) levels increased post-operatively from 7.8 ± 20.2 mg/L to 43.9 ± 55.1 mg/L (p < 0.01), and mean serum albumin decreased from 38.9 ± 4.4 g/L to 33.9 ± 5.5 g/L (p < 0.01). Mean central retinal arteriole and venular equivalent calibre (CRAE, CRVE) increased post-operatively (142.4 ± 13.3 µm to 146.4 ± 13.0 µm, p < 0.01 and 213.1 ± 16.8 µm to 217.9 ± 18.3 µm, p < 0.01, respectively). The systemic microvasculature dilates post-operatively possibly secondary to inflammation and endothelial dysfunction. These changes were present within 3 days of surgery and may confound the use of small vessel calibre to predict cardiac risk in surgical inpatients. Microvascular dilatation in response to other inflammatory stimuli such as pneumonia is a known potential confounder in hospital patients.