OBJECTIVE: To evaluate mortality differences between weekend and weekday emergency stroke admissions in England over time, and in particular, whether a reconfiguration of stroke services in Greater London was associated with a change in this mortality difference. DESIGN, SETTING AND PARTICIPANTS: Risk-adjusted difference-in-difference time trend analysis using hospital administrative data. All emergency patients with stroke admitted to English hospitals from 1 January 2008 to 31 December 2014 were included. MAIN OUTCOMES: Mortality difference between weekend and weekday emergency stroke admissions. RESULTS: We identified 507 169 emergency stroke admissions: 26% of these occurred during the weekend. The 7-day in-hospital mortality difference between weekend and weekday admissions declined across England throughout the study period. In Greater London, where the reorganisation of stroke services took place, an adjusted 28% (relative risk (RR)=1.28, 95% CI 1.09 to 1.47) higher weekend/weekday 7-day mortality ratio in 2008 declined to a non-significant 9% higher risk (RR=1.09, 95% CI 0.91 to 1.32) in 2014. For the rest of England, a 15% (RR=1.15, 95% CI 1.09 to 1.22) higher weekend/weekday 7-day mortality ratio in 2008 declined to a non-significant 3% higher risk (RR=1.03, 95% CI 0.97 to 1.10) in 2014. During the same period, in Greater London an adjusted 12% (RR=1.12, 95% CI 1.00 to 1.26) weekend/weekday 30-day mortality ratio in 2008 slightly increased to 14% (RR=1.14, 95% CI 1.00 to 1.30); however, it was not significant. In the rest of England, an 11% (RR=1.11, 95% CI 1.07 to 1.15) higher weekend/weekday 30-day mortality ratio declined to a non-significant 4% higher risk (RR=1.04, 95% CI 0.99 to 1.09) in 2014. We found no statistically significant association between decreases in the weekend/weekday admissions difference in mortality and the centralisation of stroke services in Greater London. CONCLUSIONS: There was a steady reduction in weekend/weekday differences in mortality in stroke admissions across England. It appears statistically unrelated to the centralisation of stroke services in Greater London, and is consistent with an overall national focus on improving stroke services.