Introduction Surgical site infection (SSI) is one of the most serious complications after spinal surgery. Predisposing factors as well as the long-term consequences of the SSI treated according to the current guidelines are less reported. Aims of the study were to analyze the risk factors for SSI in patients requiring routine lumbar surgery because of disc degeneration cohort and to determine the impact of SSI on long-term outcome. Reliability of the results was tested using a prospectively recruited validation cohort. Materials and Methods A total of 1,030 patients ( N = 1,030) were included in the study. All patients underwent one or two-level decompression or instrumented lumbar fusion. Patients completed self-reported health status measurement questionnaires—Oswestry Disability Index (ODI), Core Outcome Measurement Index (COMI), Zung Depression Scale (ZDS), and Modified Somatic Perception Questionnaire (MSPQ)—and visual analog scale for pain at baseline and 2 years after the surgery. SSI was defined according to the latest Centers for Disease Control and Prevention (CDC) guideline and treated according to the current recommendation of the National Orthopedic and Infectious Diseases Societies. Effect of baseline characteristics, comorbidities, pain history, and surgical data on the occurrence of SSI was determined in uni- and multivariate logistic regression models. The performance of the final multivariate regression model was assessed by measuring its discriminative ability (c-index) in ROC analysis. Five-point Likert scale on self-reported outcome was classified into two categories (“good” and “poor” result) and influence of SSI on outcome was also analyzed. SPSS 20.0 statistical program package was used for analyses where p < 0.05 was considered significant. Results The incidence of SSI in the test cohort was found 3.5% and 3.9% in the validation cohort. The significant ( p < 0.001) multivariate regression model predictive for the occurrence of SSI contained the patient's age, body mass index (BMI), and the presence of some comorbidities, such as diabetes, ischemic heart disease, arrhythmia, liver disease, and autoimmune disease. The c-index of the model was 0.71, showing good discriminative ability and it was confirmed by the data of the independent validation cohort (c = 0.72). There was no significant difference in changes of mean scores of pain and outcome questionnaires comparing patients with and without SSI (pain: p = 0.42, ODI: p = 0.79, COMI: p = 0.79). The self-reported overall outcome of the index procedure was not influenced by the occurrence of SSI (chi-square = 3.35, df = 1, p = 0.067). Conclusions No significant difference was found in the incidence of SSI in one- and two-level noninstrumented and instrumented lumbar degenerative surgeries. Predisposing factors for SSI were older age, higher BMI, and the presence of certain comorbidities. Analyzing the long-term outcome of surgical treatment, no significant difference was found if the SSI was treated according to the recent guidelines. Our predictive model for SSI was validated on an independent prospective cohort.