IMPORTANCE: Most US states have amended self-defense laws to enhance legal immunities for individuals using deadly force in public. Despite concerns that "stand your ground" (SYG) laws unnecessarily encourage the use of deadly violence, their impact on violent deaths and how this varies across states and demographic groups remains unclear. OBJECTIVE: To evaluate the association of SYG laws with homicide and firearm homicide, nationally and by state, while considering variation by the race, age, and sex of individuals who died by homicide. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a controlled, multiple-baseline and -location interrupted time series design, using natural variation in the timings and locations of SYG laws to assess associations. Changes in homicide and firearm homicide were modeled using Poisson regression analyses within a generalized additive model framework. Analyses included all US states that enacted SYG laws between 2000 and 2016 and states that did not have SYG laws enacted during the full study period, 1999 to 2017. Data were analyzed from November 2019 to December 2020. EXPOSURES: SYG self-defense laws enacted by statute between January 1, 2000, to December 31, 2016. MAIN OUTCOMES AND MEASURES: The main outcomes were statewide monthly rates of homicide and firearm-related homicide (per 100 000 persons) from January 1, 1999, to December 31, 2017, grouped by characteristics (ie, race, age, sex) of individuals who died by homicide. RESULTS: Forty-one states were analyzed, including 23 states that enacted SYG laws during the study period and 18 states that did not have SYG laws, with 248 358 homicides (43.7% individuals aged 20-34 years; 77.9% men and 22.1% women), including 170 659 firearm homicides. SYG laws were associated with a mean national increase of 7.8% in monthly homicide rates (incidence rate ratio [IRR],1.08; 95% CI, 1.04-1.12; P < .001) and 8.0% in monthly firearm homicide rates (IRR, 1.08; 95% CI, 1.03-1.13; P = .002). SYG laws were not associated with changes in the negative controls of suicide (IRR, 0.99; 95% CI, 0.98-1.01) or firearm suicide (IRR, 1.00; 95% CI, 0.98-1.02). Increases in violent deaths varied across states, with the largest increases (16.2% to 33.5%) clustering in the South (eg, Alabama, Florida, Georgia, Louisiana). There were no differential associations of SYG laws by demographic group. CONCLUSIONS AND RELEVANCE: These findings suggest that adoption of SYG laws across the US was associated with increases in violent deaths, deaths that could potentially have been avoided.