Background: Cutaneous squamous cell carcinoma (CSCC) is the 2^nd most common malignancy in the US. Approximately 10% of patients will experience either recurrent or metastatic disease, leading to worsened morbidity and mortality. In 2019, anti-PD1 therapy was FDA approved for metastatic or unresectable CSCC, and has been established as the standard frontline systemic therapy for this disease. Here we present our long-term, follow-up data investigating the efficacy, safety, and durability of PD-1 therapy for CSCC. Methods: This is a retrospective cohort study of metastatic or unresectable CSCC patients treated with PD-1 therapy at the University of Southern California Norris Comprehensive Cancer Center and the Scripps MD Anderson Cancer Center between June 2016 and January 2023. Patient demographics, tumor characteristics, and treatment related variables were collected. Objective response (ORR) was collected per RECIST criteria. Kaplan-Meier curves were used to estimate progression free survival (PFS) and overall survival (OS). For patients receiving salvage therapy post-PD1, progression free survival 2 (PFS2) and objective response rate 2 (ORR2) were also calculated. Toxicities were graded per CTCAE v5.0. Results: A total of 39 patients diagnosed with CSCC received at least one cycle of PD-1 therapy; among these 8 were excluded from efficacy analysis. Patients were on average 68 years old (range 22-97), predominantly male (69.2%) and Caucasian (74.4%). The most common primary tumor location was head/neck (64.1%), followed by extremity (15.4%). The mean tumor diameter was 6.0 cm (4.5-7.5, 95% CI). The majority of tumors were either moderately (33.3%) or poorly (28.2%) differentiated. The most common sites of metastatic disease included lymph node (41.0%), skin/soft tissue (33.3%) and bone (25.6%). Patients received on average 7 cycles of PD-1 therapy (range 1-26) and were followed for median 13.8 months. ORR for all patients was 39.0%, including CR and PR in 7 (22.6%) and 4 (13.0%) patients, respectively; 10 patients (32.2%) achieved stable disease (SD), while 7 patients (22.6%) had progression of disease (PD). Median PFS was 6.8 months, while OS was 26.7 months. Among 10 patients receiving salvage therapy after PD-1, 6 (60.0%) received a platinum-containing regimen. Median PFS2 was 4.4 months, while ORR2 was 10.0% with 1 PR, 4 SD, and 5 with PD. PD-1 therapy was well tolerated with 13 patients (33.3%) experiencing Grade 1-2 toxicity and 2 patients (5.2%) experiencing Grade 3-4. Conclusions: In this study of long-term outcomes of CSCC patients treated with PD-1 blockade, we found that initial responses to PD-1 therapy were durable, although PFS2 was less durable for patients who required salvage therapy and ORR2 was low. Novel treatment options are needed for patients with advanced CSCC who do not achieve durable responses to PD-1 based therapy.