OBJECTIVES: To assess the influence of medical representatives on prescribing practice of physicians in health facilities, Mekelle, Northern Ethiopia. METHODS: Facility-based cross-sectional study was conducted enrolling all physicians working in public and private health facilities. The data were collected from February to March, 2015. Data were then entered into Epidata Version 3.1 and transferred to STATA version 12 for analysis. Both bivariable and multivariable logistic regressions were used to determine predictors. RESULTS: Of the 90 physicians approached, 83(92%) of them responded to the interview. Sixty percent of the respondents were working in public facilities. Nearly three-fourth of physicians had experience of less than six years and 52(63%) of the respondents were general practitioners (GPs). In this study, 40 (48.2%) of the physicians believed that their prescribing decisions were influenced by visits of medical representatives (MRs). Physicians accepting gifts from MRs were six times more likely influenced than those who did not accept any gifts [AOR= 6.56, 95% CI: 2.25, 19.13]. Stationary materials 23(35.4%) and drug samples 20(54.2%) were the commonest kinds of gifts given to physicians and face to face talking 45(54.2%) was the most frequent promotional methods. The finding of this study showed that around thirty-nine percent of MRs have had negative attitude toward competitors’ product. Moreover, working in private health facility was also another predictor of influence of prescribing decision in the study area [AOR= 12.78, 95% CI: 1.31, 124.56]. CONCLUSIONS: Nearly half of the physicians working in Mekelle reported that their prescribing decisions were influenced by MRs in the last 12 months. Accepting gifts and working in private health facilities were predictors of influencing prescribing decisions. However, most MRs fails to provide adequate and accurate information regarding their products and they had a negative attitude towards the competitors` product(s).