Purpose: Chronic radiation cystitis (CRC) develops after radiation therapy and can present with symptoms like urinary frequency, urgency, pelvic pain, and nocturia. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory CRC patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months. Materials and methods: CRC patients recalcitrant to previous treatments received ABT comprised of intra-detrusor injections of 100 mg micronized AM diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, SF-12 Health Survey) were repeated at pre-op and 2, 4, 8, 12, 16, 20, 24, and 36 weeks post-injection. Results: Five consecutive patients with a mean age of 64.4 ± 20.1 years with a median CRC duration of 10 years were included and followed for 6 months. After ABT, the lower urinary tract symptoms improved as early as 2 weeks and were maintained up to 20 weeks. BPIC significantly improved from 36.6 ± 1.1 at baseline to 12.6 ± 1.5 at 16 weeks and 13.8 ± 2.9 at 20 weeks. At 24 and 36 weeks, the improvement was maintained in four (80%) of the five patients (BPIC = 13.8 ± 1.0). Uroflow assessment showed voiding volume improved two-fold in four of the five patients at 24 weeks compared to baseline. Conclusion: Our data suggest that a significant number of CRC patients may have durable benefit after ABT. Despite this, some of them can show symptoms rebound at 24 weeks.