Importance: Iowa is 1 of 5 states in the US that have not issued a stay-at-home order during the coronavirus disease 2019 (COVID-19) pandemic. There is no empirical evidence on whether issuing a stay-at-home order in Iowa could have been associated with a reduced rate of COVID-19 infections in the state.

Objective: To compare COVID-19 cases in border counties in Iowa, which did not issue a stay-at-home order, with cases in border counties in Illinois, which did issue a stay-at-home order.

Design, setting, and participants: This cross-sectional study with a difference-in-differences design compared daily changes in COVID-19 cases per 10 000 residents in 8 Iowa counties bordering Illinois with those in the 7 Illinois counties bordering Iowa before and after Illinois issued a stay-at-home order on March 21, 2020. Additional sensitivity analyses were conducted to account for differences in timing of closing schools and nonessential businesses between the 2 states and differential trends in COVID-19 cases by county population density and poverty rates.

Exposures: Issuing a stay-at-home order.

Main outcomes and measures: Comparison of cumulative cases of COVID-19 per 10 000 residents in border counties in Iowa and Illinois.

Results: The total populations were 462 445 in the Iowa border counties and 272 385 in the Illinois border counties. Population density was higher in the Iowa counties (114.2 people per square mile) than in the Illinois counties (78.2 people per square mile). Trends of cumulative COVID-19 cases per 10 000 residents for the Iowa and Illinois border counties were comparable before the Illinois stay-at-home order, which went into effect at 5:00 pm on March 21 (March 15 to March 21: 0.024 per 10 000 residents vs 0.026 per 10 000 residents). After that, cases increased more quickly in Iowa and more slowly in Illinois. Within 10, 20, and 30 days after the enactment of the stay-at-home order in Illinois, the difference in cases was -0.51 per 10 000 residents (SE, 0.09; 95% CI, -0.69 to -0.32; P < .001), -1.15 per 10 000 residents (SE, 0.49; 95% CI, -2.12 to -0.18; P = .02), and -4.71 per 10 000 residents (SE, 1.99; 95% CI, -8.64 to -0.78; P = .02), respectively. The estimates indicate excess cases in the border Iowa counties by as many as 217 cases after 1 month without a stay-at-home order. This estimate of excess cases represents 30.4% of the 716 total cases in those Iowa counties by that date. Sensitivity analyses addressing differences in timing of closing schools and nonessential businesses and differences in county population density and poverty rates between the 2 states supported these findings.

Conclusions and relevance: This cross-sectional study with a difference-in-differences design found an increase in estimated rates of COVID-19 cases per 10 000 residents in the border counties in Iowa compared with the border counties in Illinois following a stay-at-home order that was implemented in Illinois but not in Iowa.