Objective Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic management, with first line immunotherapy followed by second line immunotherapy if response to first line therapy is inadequate. Meta analysis of the evidence base may provide higher quality evidence to support this recommendation. Method We undertook a systematic review of observational cohort studies reporting autoimmune encephalitis patients treated with either second line immunotherapy or first line immunotherapy alone, and outcomes reported using the modified Rankin scale (mRS; search date: 22 April 2020). We performed several one stage multi level individual patient data (IPD) meta analyses to examine the association between second line immunotherapy and final mRS scores (PROSPERO ID CRD42020181805). Result IPD was obtained for 356 patients from 25 studies. Most studies were rated as moderate to high risk of bias. Seventy one patients (71/356, 19%) were treated with second line immunotherapy. We did not find a statistically significant association between treatment with second line immunotherapy and final mRS score for the cohort overall (odds ratio (OR) 1.74, 95% CI 0.98 3.08, p = 0.057), or sub groups with NMDA receptor encephalitis (OR 1.03, 95% CI 0.45 2.38, p = 0.944) or severe AE (maximum mRS score >2 ; OR 1.673, 95% CI 0.93 3.00, p = 0.085). Treatment with second line immunotherapy was associated with higher final mRS scores in sub groups with LGI 1 AE (OR 6.70, 95% CI 1.28 35.1, p = 0.024) and long term (at least 12 months) follow up (OR 3.94, 95% CI 1.67 9.27, p = 0.002). Significance We did not observe an association between treatment with second line immunotherapy and lower final mRS scores in patients with AE. This result should be interpreted with caution given the risk of bias, limited adjustment for disease severity, and insensitivity of the mRS in estimating psychiatric and cognitive disability.