Increased incidence of hand, foot and mouth disease (HFMD) has been recognized as a critical challenge to communicable disease control and public health response. This study aimed to quantify the association between climate variation and notified cases of HFMD in selected cities of Shanxi Province, and to provide evidence for disease control and prevention. Meteorological variables and HFMD cases data in 4 major cities (Datong, Taiyuan, Changzhi and Yuncheng) of Shanxi province, China, were obtained from the China Meteorology Administration and China CDC respectively over the period 1 January 2009 to 31 December 2013. Correlations analyses and Seasonal Autoregressive Integrated Moving Average (SARIMA) models were used to identify and quantify the relationship between the meteorological variables and HFMD. HFMD incidence varied seasonally with the majority of cases in the 4 cities occurring from May to July. Temperatures could play important roles in the incidence of HFMD in these regions. The SARIMA models indicate that a 1° C rise in average, maximum and minimum temperatures may lead to a similar relative increase in the number of cases in the 4 cities. The lag times for the effects of temperatures were identified in Taiyuan, Changzhi and Yuncheng. The numbers of cases were positively associated with average and minimum temperatures at a lag of 1 week in Taiyuan, Changzhi and Yuncheng, and with maximum temperature at a lag of 2 weeks in Yuncheng. Positive association between the temperature and HFMD has been identified from the 4 cities in Shanxi Province, although the role of weather variables on the transmission of HFMD varied in the PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003572 March 5, 2015 1 / 19 OPEN ACCESS Citation:Wei J, Hansen A, Liu Q, Sun Y, Weinstein P, Bi P (2015) The Effect of Meteorological Variables on the Transmission of Hand, Foot and Mouth Disease in Four Major Cities of Shanxi Province, China: A Time Series Data Analysis (2009-2013). PLoS Negl Trop Dis 9(3): e0003572. doi:10.1371/ journal.pntd.0003572 Editor: Rebekah Crockett Kading, Genesis Laboratories, UNITED STATES Received: September 1, 2014 Accepted: January 27, 2015 Published: March 5, 2015 Copyright: © 2015 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: This project has been partially funded by AusAID Development Research Awards Scheme 2012 (ID 66888). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. 4 cities. Relevant prevention measures and public health action are required to reduce future risks of climate change with consideration of local climatic conditions.