BackgroundThe potential impact of insulin resistance on stroke prognosis after IV thrombolysis is poorly understood. This study aimed to assess the effect of insulin resistance and metabolic syndrome on the outcome of IV thrombolysis in non-diabetic patients with acute ischaemic stroke.MethodsThis prospective observational study was conducted on 70 non-diabetic acute ischaemic stroke patients who received rt-PA within 3 h of stroke onset. Patients were subjected to baseline and follow-up NIHSS measurements at 24 h and 3 months post-treatment. Stroke outcome was assessed after 3 months using the Modified Rankin Scale (mRS). The homeostasis model assessment–insulin resistance (HOMA-IR) was calculated for the included patients at stroke onset.ResultsThe mean age of included patients was 57.04 ± 14.39 years. Patients with unfavourable outcome had a significantly higher frequency of insulin resistance and metabolic syndrome, higher values of baseline NIHSS, insulin, HOMA-IR, uric acid and lower levels of HDL than those with favourable outcome (Pvalue = 0.035, 0.007, ≤ 0.001, 0.001, ≤ 0.001, 0.002, 0.033, respectively). Each point increase in NIHSS before rt-PA increased the odds of an unfavourable outcome by 2.06 times (95% CI 1.22 − 3.478). Also, insulin resistance increased the odds of the unfavourable outcome by 11.046 times (95% CI 1.394–87.518). There was a statistically significant improvement in NIHSS 3 months after receiving rt-PA in all patients, significantly higher in patients who did not have insulin resistance or metabolic syndrome.ConclusionInsulin resistance and metabolic syndrome were associated with worse functional outcomes in non-diabetic stroke patients after receiving rt-PA.