Cutaneous squamous and basal cell carcinoma (keratinocyte carcinoma, KC) are common malignancies treated with radiotherapy (RT) to preserve form and function. Treatment of KC can compromise quality of life (QOL), but little is known about patient-reported QOL before and after RT for early KC. The purpose of this study was to assess prospectively collected patient-reported QOL before and after RT for early KC and compare this to previously reported studies of other treatments. It was hypothesized that QOL deteriorates soon after RT, with subsequent improvement of a magnitude similar to previously published reports of other KC treatments. Patients undergoing RT for early-stage (T0-2, <4 cm) KC who completed a QOL assessment before and at least once after RT were the subjects of study. Characteristics of patients, tumors and treatment were recorded. Patient-reported QOL was measured by 2 validated indices: Skindex-16 (S16, including subscales of symptoms, emotions, functioning; lower score is better QOL) and Skin Cancer Index (SCI, including emotional, social and appearance subscales; higher score is better QOL). Paired t-tests compared scores before and at 4 time points after treatment (6 weeks, 3 months, 1 and 2+ years), with a ≥10-point difference considered clinically significant, and a p<0.0125 considered statistically significant due to Bonferroni correction. A total of 85 patients (median age 79 years) with early KC, most of which were basal cell carcinomas (87%) on the face (80%) and an average of 1.3 cm in diameter were treated with a median of 48 Gy in 12 fractions. Composite S16 scores and total SCI scores showed significant, clinically meaningful improvements 3 months (15.2→5.2) and 6 weeks (72.0→85.7) after RT. Non-significant declines in QOL happened 6 weeks after treatment on the S16 symptom subscale (11.3→16.6). Concurrently, S16 and SCI emotional subscales (25.9→14.4 and 67.2→79.3) significantly improved, and this trend persisted for 2+ years. Improvements in S16 functioning (8.7→2.8) and SCI social (80.2→89.6) and appearance (68.6→90.5) QOL occurred. S16 demonstrated that 1-2 years after treatment, composite QOL improved by 45%, 47%, 39% and 10% in patients treated with RT, Mohs surgery, excision and electrodessication and curettage, respectively. SCI demonstrated that 3-4 months after treatment, total QOL improved by 24% and 4-13% after RT and Mohs surgery, respectively. QOL related to symptoms deteriorates at 6 weeks after RT, with clinically and statistically significant improvement seen by 3 months after RT. QOL related to emotions, functioning, social and appearance domains all improve after RT. The changes in QOL are similar if not greater than those observed after other treatments of early KC, and may help guide patient expectations following RT.