The US government implemented the Hospital Readmission Reduction Program on 1 October 2012 to reduce readmission rates through financial penalties to hospitals with excessive readmissions. We conducted a pooled cross-sectional analysis of US hospitals from 2009 to 2015 to determine the association of the Hospital Readmission Reduction Program with 30-day readmissions. We utilized multivariable linear regression with year and state fixed effects. The model was adjusted for hospital and market characteristics lagged by 1 year. Interaction effects of hospital and market characteristics with the Hospital Readmission Reduction Program indicator variable was also included to assess whether associations of Hospital Readmission Reduction Program with 30-day readmissions differed by these characteristics. In multivariable adjusted analysis, the main effect of the Hospital Readmission Reduction Program was a 3.80 percentage point (p < 0.001) decrease in readmission rates in 2013-2015 relative to 2009-2012. Hospitals with lower readmission rates overall included not-for-profit and government hospitals, medium and large hospitals, those in markets with a larger percentage of Hispanic residents, and population 65 years and older. Higher hospital readmission rates were observed among those with higher licensed practical nurse staffing ratio, larger Medicare and Medicaid share, and less competition. Statistically significant interaction effects between hospital/market characteristics and the Hospital Readmission Reduction Program on the outcome of 30-day readmission rates were present. Teaching hospitals, rural hospitals, and hospitals in markets with a higher percentage of residents who were Black experienced larger decreases in readmission rates. Hospitals with larger registered nurse staffing ratios and in markets with higher uninsured rate and percentage of residents with a high school education or greater experienced smaller decreases in readmission rates. Findings of the current study support the effectiveness of the Hospital Readmission Reduction Program but also point to the need to consider the ability of hospitals to respond to penalties and incentives based on their characteristics during policy development.