Concurrent chemoradiation is standard-of-care for patients with squamous cell carcinoma of the anus (SCCA). Poor compliance to chemotherapy, radiotherapy treatment interruptions and unplanned breaks may impact adversely on long-term outcomes.The ACT II trial recruited 940 patients with localized SCCA, and assigned patients to mitomycin (week 1) or cisplatin (weeks 1 and 5), with fluorouracil (weeks 1 & 5) and radiotherapy (50·4Gy in 28 fractions over 38 days). This post-hoc analysis examined the association between baseline factors (age, gender, site, T-stage and N-stage), and compliance to treatment (radiotherapy and chemotherapy), and their effects on loco-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS). Compliance was categorized into groups. Radiotherapy: 6 groups according to total dose (TD) and overall treatment time (OTT). Chemotherapy: 3 groups (A = per-protocol; B = dose reduction or delay; C = omitted).931/940 patients were evaluable for radiotherapy and 936 for chemotherapy compliance. Baseline Glomerular filtration rate (GR) <60 mL/min and cisplatin were significantly associated with poor week 5 compliance to chemotherapy (p 0.003 and 0.02, respectively). Omission of week 5 chemotherapy was associated with significantly worse LRFFS (HR 2.53 [1.33 to 4.82] p=0.005). Dose reductions/delays or omission of week 5 chemotherapy were associated with significantly worse FPFS (HR: 1.56 [95%CI: 1.18-2.06], p=0.002 and HR: 2.39 [95%CI: 1.44-3.98}, p=0.001, respectively) and OS (HR: 1.92 [95%CI: 1.41-2.63], p<0.001 and (HR: 2.88 [95%CI: 1.63-5.08], p<0.001, respectively). Receiving the target radiotherapy dose in >42 days is associated with worse PFS and OS (HR:1.72 (95%CI:1.17-2.54), p=0.006).Poor compliance to chemotherapy and radiotherapy were associated with worse LRFFS, PFS and OS. Treatment interruptions should be minimized, and OTT and TD maintained.