From September 2020 to May 2021 Madrid region (Spain) followed a rather unique non-pharmaceutical intervention (NPI) by establishing a strategy of perimeter lockdowns (PLs) that banned travels to and from areas satisfying certain epidemiological risk criteria. PLs were pursued to avoid harsher restrictions, but some studies have found that the particular implementation by Madrid authorities was rather ineffective. Based on Madrid's case, we devise a general, minimal framework to investigate the PLs effectiveness by using a data-driven metapopulation epidemiological model of a city, and explore under which circumstances the PLs could be a good NPI. The model is informed with real mobility data from Madrid to contextualize its results, but it can be generalized elsewhere. The lowest lockdown activation threshold [Formula: see text] considered (14-day cumulative incidence rate of 20 cases per every [Formula: see text] inhabitants) shows a prevalence reduction [Formula: see text] with respect to the scenario [Formula: see text], more akin to the case of Madrid, and assuming no further mitigation. Only the combination of [Formula: see text] and mobility reduction [Formula: see text] can avoid PLs for more than [Formula: see text] of the system. The combination of low [Formula: see text] and strong local transmissibility reduction is key to minimize the impact, but the latter is harder to achieve given that we assume a situation with highly mitigated transmission, resembling the one observed during the second wave of COVID-19 in Madrid. Thus, we conclude that a generalized lockdown is hard to avoid under any realistic setting if only this strategy is applied.