BACKGROUND: Primary Health Care (PHC) has been key element in detection, monitoring and treatment of COVID-19 cases in Spain. We describe how PHC practices (PCPs) organized healthcare to guarantee quality and safety and, if there were differences among the 17 Spanish regions according to the COVID-19 prevalence. METHODS: Cross-sectional study through the PRICOV-19 European Online Survey in PCPs in Spain. The questionnaire included structure and process items per PCP. Data collection was due from January to May 2021. A descriptive and comparative analysis and a logistic regression model were performed to identify differences among regions by COVID-19 prevalence (low < 5% or high ≥5%). RESULTS: Two hundred sixty-six PCPs answered. 83.8% of PCPs were in high prevalence regions. Over 70% PCPs were multi-professional teams. PCPs attended mainly elderly (60.9%) and chronic patients (53.0%). Regarding structure indicators, no differences by prevalence detected. In 77.1% of PCPs administrative staff were more involved in providing recommendations. Only 53% of PCPs had a phone protocol although 73% of administrative staff participated in phone triage. High prevalence regions offered remote assessment (20.4% vs 2.3%, p 0.004) and online platforms to download administrative documents more frequently than low prevalence (30% vs 4.7%, p < 0.001). More backup staff members were hired by health authorities in high prevalence regions, especially nurses (63.9% vs 37.8%, p < 0.001. OR:4.20 (1.01-8.71)). 63.5% of PCPs provided proactive care for chronic patients. 41.0% of PCPs recognized that patients with serious conditions did not know to get an appointment. Urgent conditions suffered delayed care in 79.1% of PCPs in low prevalence compared to 65.9% in high prevalence regions (p 0.240). A 68% of PCPs agreed on having inadequate support from the government to provide proper functioning. 61% of high prevalence PCPs and 69.5% of low ones (p: 0.036) perceived as positive the role of governmental guidelines for management of COVID-19. CONCLUSIONS: Spanish PCPs shared a basic standardized PCPs' structure and common clinical procedures due to the centralization of public health authority in the pandemic. Therefore, no relevant differences in safety and quality of care between regions with high and low prevalence were detected. Nurses and administrative staff were hired efficiently in response to the pandemic. Delay in care happened in patients with serious conditions and little follow-up for mental health and intimate partner violence affected patients was identified. Nevertheless, proactive care was offered for chronic patients in most of the PCPs.