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Key Points Question Was the introduction of the 1000-mg formulation of oral acetaminophen tablets associated with an increased number of acetaminophen-related calls to the National Poison Centre in Switzerland? Findings This cross-sectional study using a quasi-experimental interrupted time series analysis of 15 790 acetaminophen-related poisoning calls identified a significant increase in the number of calls following the date 1000-mg tablets were authorized, particularly for calls regarding accidental poisonings. The reported poisonings in the postintervention period were more likely to include doses exceeding 10 000 mg, indicating potential for severe hepatoxicity. Meaning The results of this study support the need for public health measures to restrict the availability of the 1000-mg acetaminophen tablet to minimize the potential for accidental acetaminophen-related harm., This cross-sectional study evaluates the association of adding 1000-mg acetaminophen tablets to the Swiss market with utilization and poisonings., Importance Acetaminophen (paracetamol) is among the most widely used pain medications worldwide; while safe within the therapeutic range, intake exceeding 4000 mg/d can lead to hepatotoxicity. Prior evidence suggests that limiting the availability of large quantities of acetaminophen is associated with decreased acetaminophen-related poisonings and mortality; in Switzerland, 500-mg tablets are available over-the-counter (OTC) and, as of October 2003, 1000-mg tablets are available with prescription. Objective To evaluate the association of adding 1000-mg acetaminophen tablets to the Swiss market with utilization and poisonings. Design, Setting, and Participants This cross-sectional study used a quasi-experimental interrupted time series analysis to evaluate 15 790 acetaminophen poison records from January 1, 2000, to December 31, 2018. All calls for acetaminophen-related poisonings identified from the National Swiss Poisons Centre and all sales for oral acetaminophen tablets (prescription and OTC) dispensed between January 2000 and December 2018 were included. Exposure October 3, 2003 (Q4 2003), was defined as the intervention date, corresponding to the date of market entry for 1000-mg acetaminophen tablets in Switzerland. Main Outcomes and Measures The primary outcome was the number of quarterly acetaminophen-related poison calls to the National Poison Centre. Additional outcomes included quarterly sales for acetaminophen and change in poisoning circumstances, stratified by preintervention and postintervention periods and by formulation (ie, 500-mg and 1000-mg tablets). Results Between 2000 and 2018, 15 790 acetaminophen-related poisoning calls were identified, of which 10 628 (67.3%) were regarding women, and the mean (SD) age of patients was 25.2 (18.2) years. The interrupted time series analysis identified a significant increase in the slope for the number of reported poisonings following the intervention point, particularly for accidental circumstances (z score, −3.62; P