Purpose The prescription in International Nonproprietary Names (INN) is a legal obligation for all physicians in France since January 2015. The objective of this study was to analyze the frequency and main factors of INN drug prescribing in general practice. Methods Multicenter cross-sectional study conducted with 11 interns acting as observers of 23 GP trainers between November 2015 and January 2016. Two evaluators analyzed all GPs’ drug prescriptions to identify INN or brand name prescriptions. Results The database included 4957 drugs prescribed during 1647 visits. Of these, 1462 (29.5% [95% CI 28.2–30.8%]) were prescribed only in INN. According to the multivariate analyses, the factors favoring INN prescribing were as follows: at the drug level, its initial prescribing (OR = 1.4), a nonspecific prescribing objective (OR = 1.6), its listing in the generic drug index with (OR = 7.7) or without (OR = 2.9) efficiency objective included in the payment for public health objectives (PPHO) program, and the oral route of administration (OR from 0.4 for the percutaneous route to 0.2 for the pulmonary route); at the patient level, the male gender (OR = 1.3), the age of 15 years or more (OR = 1.9), and the absence of a long-term condition (OR = 1.3); at the physician level, the reception of a public healthcare insurance representative (OR = 4.1), the nonreception of pharmaceutical sales representatives (OR = 3.0), and the urban practice environment (OR = 2.8). Conclusions In 2015, less than one third of drugs were prescribed in INN only in general practice. The use of various incentives and regulatory measures is likely to favor the prescription of INNs by practitioners.