With widespread use of antibiotics in the aquaculture industry, bacterial resistance has recently attracted increasing attention. Continuous emergence of multi-resistant bacteria has greatly threatened human and animal health, as well as the quality and safety of livestock products. To control bacterial resistance, the effect of bacterial resistance needs to be well understood. The purpose of this study was to explore the factors influencing Escherichia coli (E. coli) drug resistance in large-scale pig farms. In this study, 296 strains of E. coli isolated and identified from large-scale pig farms in Beijing were used as the research objects. In vitro drug sensitivity tests were used to determine the sensitivity to 10 antibiotics of pig-derived E. coli. SPSS logistic regression was employed to analyze the effects of the season, pig type, sampling point (medication type) and sampling location on resistance and multi-drug resistance of E. coli from pigs. The degrees of drug resistance to 10 antibiotics of the 296 strains of pig-derived E. coli were varied, their resistance rates were between 4.05 and 97.64%, and their multi-drug resistance was appalling, with the highest resistance to six antibiotics being 26.35%. The isolated strains were proven more resistant to tetracyclines, penicillin and chloramphenicol, which are commonly used for disease prevention in pig farms, and less resistant to quinolones and aminoglycosides, which are not used in pig farms. The resistance of the isolated strains in spring and summer was generally higher than that in winter. E. coli resistance in piglets, fattening pigs and sows was more serious than that in nursery and sick pigs. The results showed that the season, type of medication and type of pig had an influence on the pig-derived E. coli resistance, among which the type of medication was the most influencing factor.