OBJECTIVE: To assess if different forms of regulation lead to differences in the quality of journal advertisements. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty advertisements from family practice journals published from 2013-2015 were extracted for three countries with distinct regulatory pharmaceutical promotion systems: Australia, Canada, and the United States (US).  PRIMARY AND SECONDARY OUTCOME MEASURES: Advertisements under each regulatory system were compared concerning three domains: information included in the advertisement, references to scientific evidence, and pictorial appeals and portrayals. An overall ranking for advertisement quality among countries was determined using the first two domains as the information assessed has been associated with more appropriate prescribing.  RESULTS: Advertisements varied significantly for number of claims with quantitative benefit (Australia: 0.0 (0.0-3.0); Canada: 0.0 (0.0-5.0); US: 1.0 (0.0-6.0); p=0.01); statistical method used in reporting benefit (RRR, ARR, and NNT) (Australia: 6.7%, n=2; Canada: 10.0%, n=3; US: 36.6%, n=11; p=0.02); mention of adverse effects, warnings, or contraindications (Australia: 13.3%, n=4; Canada: 23.3%, n=7; US: 53.3%, n=16; p=0.002); equal prominence between safety and benefit information (Australia: 25.0%, n=1; Canada: 28.6%, n=2; US: 75.0%, n=12; p=0.04); and methodologic quality of references score (Australia: 0.4150 (0.25-0.70); Canada: 0.25 (0.00-0.63); US: 0.25 (0.00-0.75); p<0.001). The US ranked first, Canada second, and Australia third for overall quality of journal advertisements. Significant differences for humor appeals (Australia: 3.3%, n=1; Canada: 13.3%, n=4; US: 26.7%, n=8; p=0.04), positive emotional appeals (Australia: 26.7%, n=8; Canada: 60.0%, n=18; US: 50.0%, n=15; p=0.03), social approval portrayals (Australia: 0.0%, n=0; Canada: 0.0%, n=0; US: 10.0%, n=3; p=0.04), and lifestyle or work portrayals (Australia: 43.3%, n=13; Canada: 50.0%, n=15; US: 76.7%, n=23; p=0.02) were found among countries. CONCLUSIONS: Different regulatory systems influence journal advertisement quality concerning all measured domains. However, differences may also be attributed to other regulatory, legal, cultural, or health system factors unique to each country.