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Background. Prescribing prophylactic antibiotics before surgery is a way to prevent infection at the surgical site. This study aimed to compare the pattern of prescribing prophylactic antibiotics with the standard instructions in the general surgery ward of Shahid Sadoughi Hospital in Yazd, Iran. Methods. A descriptive cross-sectional design was employed to conduct the study. The sample was selected through random stratified sampling method using Morgan and Krejcie sampling table. Descriptive statistics, including frequency, frequency percentage, mean, standard deviation, and Chi-square were used for data analysis in the Statistical Package for the Social Sciences (SPSS) software version 23. Results. Out of 236 cases reviewed, 27.1% met the practice guidelines regarding the time, 39.4% regarding the type of preoperative prophylaxis, and 58% with respect to the duration of the prescribed postoperative antibiotics (up to 24 hours after surgery). Conclusion. The most important reasons for the inconsistency of prophylactic antibiotics with the standard guideline include the inappropriate timing of prophylactic antibiotics and the use of antibiotics not recommended in the clinical guidelines. Informing and educating the public on the content of the notification instructions, establishing a monitoring system, and increasing the participation level of the hospital pharmacy in the distribution of medicine can be effective in prescribing prophylactic antibiotics.