Several in-person and remote delivery formats of cognitive-behavioural therapy (CBT) for panic disorder are available, but up-to-date and comprehensive evidence on their comparative efficacy and acceptability is lacking. Our aim was to evaluate the comparative efficacy and acceptability of all CBT delivery formats to treat panic disorder. To answer our question we performed a systematic review and network meta-analysis of randomised controlled trials. We searched MEDLINE, Embase, PsycINFO, and CENTRAL, from inception to 1st January 2022. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO. We found a total of 74 trials with 6699 participants. Evidence suggests that face-to-face group [standardised mean differences (s.m.d.) −0.47, 95% confidence interval (CI) −0.87 to −0.07; CINeMA = moderate], face-to-face individual (s.m.d. −0.43, 95% CI −0.70 to −0.15; CINeMA = Moderate), and guided self-help (SMD −0.42, 95% CI −0.77 to −0.07; CINeMA = low), are superior to treatment as usual in terms of efficacy, whilst unguided self-help is not (SMD −0.21, 95% CI −0.58 to −0.16; CINeMA = low). In terms of acceptability (i.e. all-cause discontinuation from the trial) CBT delivery formats did not differ significantly from each other. Our findings are clear in that there are no efficacy differences between CBT delivered as guided self-help, or in the face-to-face individual or group format in the treatment of panic disorder. No CBT delivery format provided high confidence in the evidence at the CINeMA evaluation.