Seventy-two patients 18 years or older scheduled to undergo a lower extremity surgery were included in this study comparing vapocoolant spray application prior to low-molecular weight heparin (LMWH) injection vs. a placebo water spray prior to LMWH injection. Patients received two LMWH injections, in the right arm on day 1 and the left arm on day 2, and were randomized to receive either vapocoolant spray or water spray first, followed by the opposite intervention on the 2nd day. Outcomes of interest included the following: pain measured using the Visual Analogue Scale (VAS), the incidence and diameter size of ecchymosis on injection site, and the incidence of hematoma, which were evaluated 48-hours post-injection. Results of this study demonstrated that mean VAS pain scores were statistically significantly lower in the vapocoolant spray group compared to placebo (p=0.04). However, all other measures were not statistically significantly different between the 2 groups at any timepoints (p>0.05 for all). No cases of hematoma on the injection site was observed in any of the patients. 4 patients reported temporary skin rash as a result of the vapocoolant spray.